EP1682899A2 - METHOD FOR DISTINGUISHING AML SUBTYPE INV(3)(q21q26)/t(3;3)(q21q26) FROM OTHER AML SUBTYPES - Google Patents

METHOD FOR DISTINGUISHING AML SUBTYPE INV(3)(q21q26)/t(3;3)(q21q26) FROM OTHER AML SUBTYPES

Info

Publication number
EP1682899A2
EP1682899A2 EP04797588A EP04797588A EP1682899A2 EP 1682899 A2 EP1682899 A2 EP 1682899A2 EP 04797588 A EP04797588 A EP 04797588A EP 04797588 A EP04797588 A EP 04797588A EP 1682899 A2 EP1682899 A2 EP 1682899A2
Authority
EP
European Patent Office
Prior art keywords
aml
numbers
value
inv
expression
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP04797588A
Other languages
German (de)
French (fr)
Inventor
Torsten Haferlach
Martin Dugas
Wolfgang Kern
Alexander Kohlmann
Susanne Schnittger
Claudia Schoch
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
F Hoffmann La Roche AG
Roche Diagnostics GmbH
Original Assignee
F Hoffmann La Roche AG
Roche Diagnostics GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by F Hoffmann La Roche AG, Roche Diagnostics GmbH filed Critical F Hoffmann La Roche AG
Priority to EP04797588A priority Critical patent/EP1682899A2/en
Publication of EP1682899A2 publication Critical patent/EP1682899A2/en
Withdrawn legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407Specifically defined cancers
    • G01N33/57426Specifically defined cancers leukemia
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/112Disease subtyping, staging or classification
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/158Expression markers

Definitions

  • the present invention is directed to a method for distinguishing AML subtype inv(3)(q21q26)/t(3;3)(q21q26) (abbreviated: AML_inv(3)) from other AML subtypes, in particular from t(8;21), t(15;17), inv(16), t(l lq23)/MLL (abbreviated: AML_llq23), AML_normal (normal karyotype) and/or AML_CA (complex aberrant karyotype) by determining the expression level of selected marker genes.
  • Leukemias are classified into four different groups or types: acute myeloid (AML), acute lymphatic (ALL), chronic myeloid (CML) and chronic lymphatic leukemia (CLL). Within these groups, several subcategories can be identified further using a panel of standard techniques as described below. These different subcategories in leukemias are associated with varying clinical outcome and therefore are the basis for different treatment strategies. The importance of highly specific classification may be illustrated in detail further for the AML as a very heterogeneous group of diseases. Effort is aimed at identifying biological entities and to distinguish and classify subgroups of AML which are associated with a favorable, intermediate or unfavorable prognosis, respectively.
  • the FAB classification was proposed by the French-American-British co-operative group which was based on cytomorphology and cytochemistry in order to separate AML subgroups according to the morphological appearance of blasts in the blood and bone marrow.
  • genetic abnormalities occurring in the leukemic blast had a major impact on the morphological picture and even more on the prognosis.
  • the karyotype of the leukemic blasts is the most important independent prognostic factor, regarding response to therapy as well as survival.
  • leukemia diagnostics Analysis of the morphology and cytochemistry of bone marrow blasts and peripheral blood cells is necessary to establish the diagnosis, hi some cases the addition of immunophenotyping is mandatory to separate very undifferentiated AML from acute lymphoblastic leukemia and CLL.
  • Leukemia subtypes investigated can be diagnosed by cytomorphology alone, only if an expert reviews the smears.
  • a genetic analysis based on chromosome analysis, fluorescence in situ hybridization or RT- PCR and immunophenotyping is required in order to assign all cases into the right category. The aim of these techniques besides diagnosis is mainly to determine the prognosis of the leukemia.
  • CML chronic myeloid leukemia
  • CLL chronic lymphoblastic
  • AML acute myeloid leukemia
  • the new therapeutic drug (STI571, Imatinib) inhibits the CML specific chimeric tyrosine kinase BCR-ABL generated from the genetic defect observed in CML, the BCR-ABL-rearrangement due to the translocation between chromosomes 9 and 22 (t(9;22) (q34; qll)).
  • the therapy response is dramatically higher as compared to all other drugs that had been used so far.
  • Another example is the subtype of acute myeloid leukemia AML M3 and its variant M3v both with karyotype t[15;17)(q22; ql l-12).
  • the introduction of a new drug has improved the outcome in this subgroup of patient from about 50% to 85 % long-term survivors.
  • diagnostics today must accomplish sub-classification with maximal precision. Not only for these subtypes but also for several other leukemia subtypes different treatment approaches could improve outcome. Therefore, rapid and precise identification of distinct leukemia subtypes is the future goal for diagnostics.
  • the technical problem underlying the present invention was to provide means for leukemia diagnostics which overcome at least some of the disadvantages of the prior art diagnostic methods, in particular encompassing the time-consuming and unreliable combination of different methods and which provides a rapid assay to unambiguously distinguish one AML subtype from another, e.g. by genetic analysis.
  • WO-A 03/039443 discloses marker genes the expression levels of which are characteristic for certain leukemia, e.g. AML subtypes and additionally discloses methods for differentiating between the subtype of AML cells by determining the expression profile of the disclosed marker genes.
  • WO-A 03/039443 does not provide guidance which set of distinct genes discriminate between two subtypes and, as such, can be routineously taken in order to distinguish one AML subtype from another.
  • the problem is solved by the present invention, which provides a method for distinguishing AML subtype AML_inv(3) from other AML subtypes in a sample, the method comprising determining the expression level of markers selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4, wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.1 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.1 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.2 having a negative fc value, and/or a higher expression of at least one
  • AML_inv(3) AML with inversion 3
  • AML_t(8;21) AML with t(8;21) translocation
  • AML_t(15;17) AML with t(15;17) translocation
  • AML_inv(16) AML with inversion 16
  • AML_l lq23 t(llq23)/MLL
  • AMLjtiormal AML with normal karytype.
  • all other subtypes refer to the subtypes of the present invention, the one which is under investigation versus the all others being included in the present invention.
  • a sample means any biological material containing genetic information in the form of nucleic acids or proteins obtainable or obtained from an individual.
  • the sample includes e.g. tissue samples, cell samples, bone marrow and/or body fluids such as blood, saliva, semen.
  • the sample is blood or bone marrow, more preferably the sample is bone marrow.
  • a general method for isolating and preparing nucleic acids from a sample is outlined in Example 3.
  • the term "lower expression” is generally assigned to all by numbers and Affymetrix Identification Numbers (ID), definable polynucleotides the t-values and fold change (fc) values of which are negative, as indicated in the Tables. Accordingly, the term “higher expression” is generally assigned to all by numbers and Affymetrix Id. definable polynucleotides the t- values and fold change (fc) values of which are positive.
  • ID Affymetrix Identification Numbers
  • fc fold change
  • the term "expression” refers to the process by which mRNA or a polypeptide is produced based on the nucleic acid sequence of a gene, i.e.illerexpression" also includes the formation of mRNA upon transcription.
  • the term crizdetermining the expression level preferably refers to the determination of the level of expression, namely of the markers.
  • marker refers to any genetically controlled difference which can be used in the genetic analysis of a test versus a control sample, for the purpose of assigning the sample to a defined genotype or phenotype.
  • markers refer to genes which are differentially expressed in, e.g., different AML subtypes.
  • the markers can be defined by their gene symbol name, their encoded protein name, their transcript identification number (cluster identification number), the data base accession number, public accession number or GenBank identifier or, as done in the present invention, Affymetrix identification number, chromosomal location, UniGene accession number and cluster type, LocusLink accession number (see Examples and Tables).
  • the Affymetrix identification number (affy id) is accessible for anyone and the person skilled in the art by entering the "gene expression omnibus" internet page of the National Center for Biotechnology Information (NCBI) (http://www.ncbi.nlm.nih.gov/geo/).
  • NCBI National Center for Biotechnology Information
  • the affy id's of the polynucleotides used for the method of the present invention are derived from the so-called U133 chip.
  • the expression level of a marker is determined by the determining the expression of its corresponding "polynucleotide" as described hereinafter.
  • the term “bigpolynucleotide” refers, generally, to a DNA, in particular cDNA, or RNA, in particular a cRNA, or a portion thereof or a polypeptide or a portion thereof.
  • the polynucleotide is formed upon transcription of a nucleotide sequence which is capable of expression.
  • the polynucleotide fragments refer to fragments preferably of between at least 8, such as 10, 12, 15 or 18 nucleotides and at least 50, such as 60, 80, 100, 200 or 300 nucleotides in length, or a complementary sequence thereto, representing a consecutive stretch of nucleotides of a gene, cDNA or mRNA.
  • polynucleotides include also any fragment (or complementary sequence thereto) of a sequence derived from any of the markers defined above as long as these fragments unambiguously identify the marker.
  • the determination of the expression level may be effected at the transcriptional or translational level, i.e. at the level of mRNA or at the protein level.
  • Protein fragments such as peptides or polypeptides advantageously comprise between at least 6 and at least 25, such as 30, 40, 80, 100 or 200 consecutive amino acids representative of the corresponding full length protein. Six amino acids are generally recognized as the lowest peptidic stretch giving rise to a linear epitope recognized by an antibody, fragment or derivative thereof.
  • the proteins or fragments thereof may be analysed using nucleic acid molecules specifically binding to three-dimensional structures (aptamers).
  • the determination of the expression levels may be effected by a variety of methods.
  • the polynucleotide, in particular the cRNA is labelled.
  • the labelling of the polynucleotide or a polypeptide can occur by a variety of methods known to the skilled artisan.
  • the label can be fluorescent, chemiluminescent, bioluminescent, radioactive (such as 3 H or 32 P).
  • the labelling compound can be any labelling compound being suitable for the labelling of polynucleotides and/or polypeptides.
  • fluorescent dyes such as fluorescein, dichlorofluorescein, hexachlorofluorescein, BODIPY variants, ROX, tetramethylrhodamin, rhodamin X, Cyanine-2, Cyanine-3, Cyanine-5, Cyanine-7, IRD40, FluorX, Oregon Green, Alexa variants (available e.g. from Molecular Probes or Amersham Biosciences) and the like, biotin or biotinylated nucleotides, digoxigenin, radioisotopes, antibodies, enzymes and receptors.
  • fluorescent dyes such as fluorescein, dichlorofluorescein, hexachlorofluorescein, BODIPY variants, ROX, tetramethylrhodamin, rhodamin X, Cyanine-2, Cyanine-3, Cyanine-5, Cyanine-7, IRD40, FluorX, Oregon Green, Alexa variants (available e
  • the detection is done via fluorescence measurements, conjugation to streptavidin and/or avidin, antigen-antibody- and/or antibody-antibody- interactions, radioactivity measurements, as well as catalytic and/or receptor/ligand interactions.
  • Suitable methods include the direct labelling (incorporation) method, the amino-modified (amino-allyl) nucleotide method (available e.g. from Ambion), and the primer tagging method (DNA dendrimer labelling, as kit available e.g. from Genisphere).
  • Particularly preferred for the present invention is the use of biotin or biotinylated nucleotides for labelling, with the latter being directly incorporated into, e.g. the cRNA polynucleotide by in vitro transcription.
  • cDNA may be prepared into which a detectable label, as exemplified above, is incorporated. Said detectably labelled cDNA, in single-stranded form, may then be hybridised, preferably under stringent or highly stringent conditions to a panel of single-stranded oligonucleotides representing different genes and affixed to a solid support such as a chip. Upon applying appropriate washing steps, those cDNAs will be detected or quantitatively detected that have a counterpart in the oligonucleotide panel.
  • the mRNA or the cDNA may be amplified e.g.
  • the cDNAs are transcribed into cRNAs prior to the hybridisation step wherein only in the transcription step a label is incorporated into the nucleic acid and wherein the cRNA is employed for hybridisation.
  • the label may be attached subsequent to the transcription step.
  • proteins from a cell or tissue under investigation may be contacted with a panel of aptamers or of antibodies or fragments or derivatives thereof.
  • the antibodies etc. may be affixed to a solid support such as a chip.
  • Binding of proteins indicative of an AML subtype may be verified by binding to a detectably labelled secondary antibody or aptamer.
  • a detectably labelled secondary antibody or aptamer For the labelling of antibodies, it is referred to Harlow and Lane, "Antibodies, a laboratory manual", CSH Press, 1988, Cold Spring Harbor.
  • a minimum set of proteins necessary for diagnosis of all AML subtypes may be selected for creation of a protein array system to make diagnosis on a protein lysate of a diagnostic bone marrow sample directly.
  • Array Systems for the detection of specific protein expression profiles already are available (for example: Bio-Plex, BIORAD, M ⁇ nchen, Germany).
  • antibodies against the proteins have to be produced and immobilized on a platform e.g. glasslides or microtiterplates.
  • the immobilized antibodies can be labelled with a reactant specific for the certain target proteins as discussed above.
  • the reactants can include enzyme substrates, DNA, receptors, antigens or antibodies to create for example a capture sandwich immunoassay.
  • the expression of more than one of the above defined markers is determined.
  • the statistical significance of markers as expressed in q or p values based on the concept of the false discovery rate is determined. In doing so, a measure of statistical significance called the q value is associated with each tested feature.
  • the q value is similar to the p value, except it is a measure of significance in terms of the false discovery rate rather than the false positive rate (Storey JD and
  • markers as defined in Tables 1- 4 having a q- value of less than 3E-06, more preferred less than 1.5E-09, most preferred less than 1.5E-11, less than 1.5E-20, less than 1.5E-30, are measured.
  • the expression level of at least two, preferably of at least ten, more preferably of at least 25, most preferably of 50 of at least one of the Tables of the markers is determined.
  • the expression level of at least 2, of at least 5, of at least 10 out of the markers having the numbers 1 - 10, 1-20, 1-40, 1-50 of at least one of the Tables are measured.
  • the level of the expression of the penalmarker i.e. the expression of the polynucleotide is indicative of the AML subtype of a cell or an organism.
  • the level of expression of a marker or group of markers is measured and is compared with the level of expression of the same marker or the same group of markers from other cells or samples. The comparison may be effected in an actual experiment or in silico.
  • expression level also referred to as expression pattern or expression signature (expression profile)
  • the difference at least is 5 %, 10% or 20%, more preferred at least 50% or may even be as high as 75% or 100%. More preferred the difference in the level of expression is at least 200%, i.e. two fold, at least 500%, i.e. five fold, or at least 1000%, i.e. 10 fold.
  • the expression level of markers expressed lower in a first subtype than in at least one second subtype, which differs from the first subtype is at least 5 %, 10% or 20%, more preferred at least 50% or may even be 75% or 100%, i.e.
  • the expression level of markers expressed higher in a first subtype than in at least one second subtype, which differs from the first subtype is at least 5 %, 10% or 20%, more preferred at least 50% or may even be 75% or 100%, i.e. 2-fold higher, preferably at least 10-fold, more preferably at least 50-fold, and most preferably at least 100-fold higher in the first subtype.
  • the sample is derived from an individual having leukaemia, preferably AML.
  • the polynucleotide the expression level of which is determined is in form of a transcribed polynucleotide.
  • a particularly preferred transcribed polynucleotide is an mRNA, a cDNA and/or a cRNA, with the latter being preferred.
  • Transcribed polynucleotides are isolated from a sample, reverse transcribed and/or amplified, and labelled, by employing methods well-known the person skilled in the art (see Example 3).
  • the step of determining the expression profile further comprises amplifying the transcribed polynucleotide.
  • the method comprises hybridizing the transcribed polynucleotide to a complementary polynucleotide, or a portion thereof, under stringent hybridization conditions, as described hereinafter.
  • hybridizing means hybridization under conventional hybridization conditions, preferably under stringent conditions as described, for example, in Sambrook, J., et al, in "Molecular Cloning: A Laboratory Manual” (1989), Eds. J. Sambrook, E. F. Fritsch and T. Maniatis, Cold Spring Harbour Laboratory Press, Cold Spring Harbour, NY and the further definitions provided above.
  • Such conditions are, for example, hybridization in 6x SSC, pH 7.0 / 0.1% SDS at about
  • the salt concentration in the washing step can for example be chosen between 2x SSC/0.1% SDS at room temperature for low stringency and 0.2x SSC/0.1% SDS at 50°C for high stringency.
  • the temperature of the washing step can be varied between room temperature, ca. 22°C, for low stringency, and 65 °C to 70° C for high stringency. Also contemplated are polynucleotides that hybridize at lower stringency hybridization conditions.
  • Changes in the stringency of hybridization and signal detection are primarily accomplished through the manipulation, preferably of formamide concentration (lower percentages of formamide result in lowered stringency), salt conditions, or temperature.
  • washes performed following stringent hybridization can be done at higher salt concentrations (e.g. 5x SSC).
  • Variations in the above conditions may be accomplished through the inclusion and/or substitution of alternate blocking reagents used to suppress background in hybridization experiments.
  • the inclusion of specific blocking reagents may require modification of the hybridization conditions described above, due to problems with compatibility.
  • "Complementary” and “complementarity”, respectively, can be described by the percentage, i.e. proportion, of nucleotides which can form base pairs between two polynucleotide strands or within a specific region or domain of the two strands.
  • complementary nucleotides are, according to the base pairing rules, adenine and thymine (or adenine and uracil), and cytosine and guanine.
  • Complementarity may be partial, in which only some of the nucleic acids' bases are matched according to the base pairing rules. Or, there may be a complete or total complementarity between the nucleic acids. The degree of complementarity between nucleic acid strands has effects on the efficiency and strength of hybridization between nucleic acid strands.
  • Two nucleic acid strands are considered to be 100% complementary to each other over a defined length if in a defined region all adenines of a first strand can pair with a thymine (or an uracil) of a second strand, all guanines of a first strand can pair with a cytosine of a second strand, all thymine (or uracils) of a first strand can pair with an adenine of a second strand, and all cytosines of a first strand can pair with a guanine of a second strand, and vice versa.
  • the degree of complementarity is determined over a stretch of 20, preferably 25, nucleotides, i.e.
  • a 60% complementarity means that within a region of 20 nucleotides of two nucleic acid strands 12 nucleotides of the first strand can base pair with 12 nucleotides of the second strand according to the above ruling, either as a stretch of 12 contiguous nucleotides or interspersed by non-pairing nucleotides, when the two strands are attached to each other over said region of 20 nucleotides.
  • the degree of complementarity can range from at least about 50% to full, i.e. 100% complementarity.
  • Two single nucleic acid strands are said to be "substantially complementary" when they are at least about 80% complementary, preferably about 90% or higher. For carrying out the method of the present invention substantial complementarity is preferred.
  • Preferred methods for detection and quantification of the amount of polynucleotides i.e. for the methods according to the invention allowing the determination of the level of expression of a marker, are those described by Sambrook et al. (1989) or real time methods known in the art as the TaqMan® method disclosed in WO92/02638 and the corresponding U.S. 5,210,015, U.S.
  • the (at least one) target nucleic acid component is detected by a process comprising contacting the sample with an oligonucleotide containing a sequence complementary to a region of the target nucleic acid component and a labeled oligonucleotide containing a sequence complementary to a second region of the same target nucleic acid component sequence strand, but not including the nucleic acid sequence defined by the first oligonucleotide, to create a mixture of duplexes during hybridization conditions, wherein the duplexes comprise the target nucleic acid annealed to the first oligonucleotide and to the labeled oligonucleotide such that the 3 '-end of the first oligonucleotide is adjacent to the 5 '-end of the labeled oligonucleotide.
  • this mixture is treated with a template-dependent nucleic acid polymerase having a 5' to 3' nuclease activity under conditions sufficient to permit the 5' to 3' nuclease activity of the polymerase to cleave the annealed, labeled oligonucleotide and release labeled fragments.
  • the signal generated by the hydrolysis of the labeled oligonucleotide is detected and/ or measured.
  • TaqMan® technology eliminates the need for a solid phase bound reaction complex to be formed and made detectable.
  • Example 3 A preferred protocol if the marker, i.e. the polynucleotide, is in form of a transcribed nucleotide, is described in Example 3, where total RNA is isolated, cDNA and, subsequently, cRNA is synthesized and biotin is incorporated during the transcription reaction.
  • the purified cRNA is applied to commercially available arrays which can be obtained e.g. from Affymetrix.
  • the hybridized cRNA is detected according to the methods described in Example 3.
  • the arrays are produced by photolithography or other methods known to experts skilled in the art e.g. from U.S. 5,445,934, U.S. 5,744,305, U.S. 5,700,637, U.S. 5,945,334 and EP 0 619 321 or EP 0 373 203, or as decribed hereinafter in greater detail.
  • the polynucleotide or at least one of the polynucleotides is in form of a polypeptide.
  • the expression level of the polynucleotides or polypeptides is detected using a compound which specifically binds to the polynucleotide of the polypeptide of the present invention.
  • specifically binding means that the compound is capable of discriminating between two or more polynucleotides or polypeptides, i.e. it binds to the desired polynucleotide or polypeptide, but essentially does not bind unspecifically to a different polynucleotide or polypeptide.
  • the compound can be an antibody, or a fragment thereof, an enzyme, a so-called small molecule compound, a protein-scaffold, preferably an anticalin.
  • the compound specifically binding to the polynucleotide or polypeptide is an antibody, or a fragment thereof.
  • an "antibody” comprises monoclonal antibodies as first described by Kohler and Milstein in Nature 278 (1975), 495-497 as well as polyclonal antibodies, i.e. antibodies contained in a polyclonal antiserum.
  • Monoclonal antibodies include those produced by transgenic mice. Fragments of antibodies include F(ab') , Fab and Fv fragments. Derivatives of antibodies include scFvs, chimeric and humanized antibodies. See, for example Harlow and Lane, loc. cit.
  • the person skilled in the art is aware of a variety of methods, all of which are included in the present invention.
  • Examples include immunoprecipitation, Western blotting, Enzyme-linked immuno sorbent assay (ELISA), Enzyme-linked immuno sorbent assay (RIA), dissociation-enhanced lanthanide fluoro immuno assay (DELFIA), scintillation proximity assay (SPA).
  • ELISA Enzyme-linked immuno sorbent assay
  • RIA Enzyme-linked immuno sorbent assay
  • DELFIA dissociation-enhanced lanthanide fluoro immuno assay
  • SPA scintillation proximity assay
  • the method for distinguishing AML subtype AML_inv(3) from other AML subtypes preferably from t(8;21), t(15;17), inv(16), t(l lq23)/MLL, and/or AML_normal is carried out on an array.
  • an "array” or “microarray” refers to a linear or two- or three dimensional arrangement of preferably discrete nucleic acid or polypeptide probes which comprises an intentionally created collection of nucleic acid or polypeptide probes of any length spotted onto a substrate/solid support.
  • a collection of nucleic acids or polypeptide spotted onto a substrate/solid support also under the term "array”.
  • a microarray usually refers to a miniaturised array arrangement, with the probes being attached to a density of at least about 10, 20, 50, 100 nucleic acid molecules referring to different or the same genes per cm 2 .
  • an array can be referred to as "gene chip”.
  • the array itself can have different formats, e.g. libraries of soluble probes or libraries of probes tethered to resin beads, silica chips, or other solid supports.
  • the process of array fabrication is well-known to the person skilled in the art.
  • the process for preparing a nucleic acid array comprises preparing a glass (or other) slide (e.g. chemical treatment of the glass to enhance binding of the nucleic acid probes to the glass surface), obtaining DNA sequences representing genes of a genome of interest, and spotting sequences these sequences of interest onto glass slide.
  • Sequences of interest can be obtained via creating a cDNA library from an mRNA source or by using publicly available databases, such as GeneBank, to annotate the sequence information of custom cDNA libraries or to identify cDNA clones from previously prepared libraries.
  • the liquid containing the amplified probes can be deposited on the array by using a set of microspotting pins. Ideally, the amount deposited should be uniform.
  • the process can further include UV-crosslinking in order to enhance immobilization of the probes on the array.
  • the array is a high density oligonucleotide (oligo) array using a light-directed chemical synthesis process, employing the so-called photolithography technology.
  • oligo arrays are a high density oligonucleotide (oligo) array using a light-directed chemical synthesis process, employing the so-called photolithography technology.
  • oligo arrays are a high density oligonucleotide (oligo) array using a light-directed chemical synthesis process, employing the so-called photolithography technology.
  • oligo arrays Unlike common cDNA arrays, oligo arrays
  • the sequence can be synthesized directly onto the array, thus, bypassing the need for physical intermediates, such as PCR products, required for making cDNA arrays.
  • the marker, or partial sequences thereof can be represented by 14 to 20 features, preferably by less than
  • oligonucleotide which is a perfect match (PM) to a segment of the respective gene.
  • PM oligonucleotide are paired with mismatch (MM) oligonucleotides which have a single mismatch at the central base of the nucleotide and are used as
  • controls The chip exposure sites are defined by masks and are deprotected by the use of light, followed by a chemical coupling step resulting in the synthesis of one nucleotide. The masking, light deprotection, and coupling process can then be repeated to synthesize the next nucleotide, until the nucleotide chain is of the specified length.
  • the method of the present invention is carried out in a robotics system including robotic plating and a robotic liquid transfer system, e.g. using microfluidics, i.e. channelled structured.
  • a particular preferred method according to the present invention is as follows:
  • RNA preferably mRNA
  • the present invention is directed to the use of at least one marker selected from the markers identifiable by their Affymetrix Identification
  • AML_inv(3) Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4, for the manufacturing of a diagnostic for distinguishing AML subtype AML_inv(3) from other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(l lq23)/MLL, and/or AML_normal.
  • the use of the present invention is particularly advantageous for distinguishing AML subtype AML_inv(3) from other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(l lq23)/MLL, and/or AML_normal in an individual having AML.
  • markers for diagnosis of WHO classified leukemia subtypes preferably based on microarray technology, offers the following advantages: (1) more rapid and more precise diagnosis, (2) easy to use in laboratories without specialized experience, (3) abolishes the requirement for analyzing viable cells for chromosome analysis (transport problem), and (4) very experienced hematologists for cytomorphology and cytochemistry, immunophenotyping as well as cytogeneticists and molecularbiologists are no longer required.
  • the present invention refers to a diagnostic kit containing at least one marker selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4, for distinguishing AML subtype AML_inv(3) from other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(l lq23)/MLL, and/or AML_normal, in combination with suitable auxiliaries.
  • suitable auxiliaries include buffers, enzymes, labelling compounds, and the like.
  • the marker contained in the kit is a nucleic acid molecule which is capable of hybridizing to the mRNA corresponding to at least one marker of the present invention.
  • the at least one nucleic acid molecule is attached to a solid support, e.g. a polystyrene microtiter dish, nitrocellulose membrane, glass surface or to non-immobilized particles in solution.
  • the diagnostic kit contains at least one reference for an AML subtype AML_inv(3) and/or any other AML subtype, preferably from t(8;21), t(15;17), inv(16), t(llq23)/MLL, and/or AML_normal.
  • the reference can be a sample or a data bank.
  • the present invention is directed to an apparatus for distinguishing AML subtype AML_inv(3) from other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(l lq23)/MLL, and/or AML_normal in a sample, containing a reference data bank obtainable by comprising (a) compiling a gene expression profile of a patient sample by determining the expression level at least one marker selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4 and (b) classifying the gene expression profile by means of a machine learning algorithm.
  • a reference data bank obtainable by comprising (a) compiling a gene expression profile of a patient sample by determining the expression level at least one marker selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4 and (b) classifying the gene expression profile by means of a machine learning
  • the "machine learning algorithm” is a computational-based prediction methodology, also known to the person skilled in the art as “classifier”, employed for characterizing a gene expression profile.
  • the signals corresponding to a certain expression level which are obtained by the microarray hybridization are subjected to the algorithm in order to classify the expression profile.
  • Supervised learning involves "training” a classifier to recognize the distinctions among classes and then “testing” the accuracy of the classifier on an independent test set. For new, unknown samples the classifier shall predict into which class the sample belongs.
  • the machine learning algorithm is selected from the group consisting of Weighted Voting, K-Nearest Neighbors, Decision Tree Induction, Support Vector Machines (SVM), and Feed-Forward Neural Networks.
  • the machine learning algorithm is Support Vector Machine, such as polynomial kernel and Gaussian Radial Basis Function-kernel SVM models.
  • the classification accuracy of a given gene list for a set of microarray experiments is preferably estimated using Support Vector Machines (SVM), because there is evidence that SVM-based prediction slightly outperforms other classification techniques like k-Nearest Neighbors (k-NN).
  • SVM Support Vector Machines
  • the LIB SVM software package version 2.36 was used (SVM-type: C-SVC, linear kernel (http://www.csie.nm.edu.tw/ ⁇ cjlin/libsvm )).
  • SVM-type C-SVC, linear kernel (http://www.csie.nm.edu.tw/ ⁇ cjlin/libsvm )).
  • the skilled artisan is furthermore referred to Brown et al., Proc.Natl.Acad.Sci., 2000; 97: 262-267, Furey et al, Bioinformatics. 2000; 16: 906-914, and Vapnik V. Statistical Learning Theory. New York:
  • the classification accuracy of a given gene list for a set of microarray experiments can be estimated using Support Vector Machines (SVM) as supervised learning technique.
  • SVMs are trained using differentially expressed genes which were identified on a subset of the data and then this trained model is employed to assign new samples to those trained groups from a second and different data set. Differentially expressed genes were identified applying ANOVA and t-test-statistics (Welch t-test). Based on identified distinct gene expression signatures respective training sets consisting of 2/3 of cases and test sets with 1/3 of cases to assess classification accuracies are designated. Assignment of cases to training and test set is randomized and balanced by diagnosis. Based on the training set a Support Vector Machine (SVM) model is built.
  • SVM Support Vector Machine
  • the apparent accuracy i.e. the overall rate of correct predictions of the complete data set was estimated by lOfold cross validation.
  • This means that the data set was divided into 10 approximately equally sized subsets, an SVM-model was trained for 9 subsets and predictions were generated for the remaining subset. This training and prediction process was repeated 10 times to include predictions for each subset. Subsequently the data set was split into a training set, consisting of two thirds of the samples, and a test set with the remaining one third. Apparent accuracy for the training set was estimated by lOfold cross validation (analogous to apparent accuracy for complete set). A SVM-model of the training set was built to predict diagnosis in the independent test set, thereby estimating true accuracy of the prediction model. This prediction approach was applied both for overall classification (multi-class) and binary classification (diagnosis X > yes or no). For the latter, sensitivity and specificity were calculated:
  • the reference data bank is backed up on a computational data memory chip which can be inserted in as well as removed from the apparatus of the present invention, e.g. like an interchangeable module, in order to use another data memory chip containing a different reference data bank.
  • the apparatus of the present invention containing a desired reference data bank can be used in a way such that an unknown sample is, first, subjected to gene expression profiling, e.g. by microarray analysis in a manner as described supra or in the art, and the expression level data obtained by the analysis are, second, fed into the apparatus and compared with the data of the reference data bank obtainable by the above method.
  • the apparatus suitably contains a device for entering the expression level of the data, for example a control panel such as a keyboard.
  • the results, whether and how the data of the unknown sample fit into the reference data bank can be made visible on a provided monitor or display screen and, if desired, printed out on an incorporated of connected printer.
  • the apparatus of the present invention is equipped with particular appliances suitable for detecting and measuring the expression profile data and, subsequently, proceeding with the comparison with the reference data bank.
  • the apparatus of the present invention can contain a gripper arm and/or a tray which takes up the microarray containing the hybridized nucleic acids.
  • the present invention refers to a reference data bank for distinguishing AML subtype AML_inv(3) from other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(llq23)/MLL, and/or AMLjtiormal in a sample obtainable by comprising (a) compiling a gene expression profile of a patient sample by determining the expression level of at least one marker selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4, and (b) classifying the gene expression profile by means of a machine learning algorithm.
  • affymetrix Identification Numbers affy id
  • the reference data bank is backed up and/or contained in a computational memory data chip.
  • Tables 1.1-4.10 show AML subtype analysis of AML subtype AML_inv(3) and other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(llq23)/MLL, and/or AML_normal.
  • the analysed markers are ordered according to their q- values, beginning with the lowest q-values.
  • Tables 1.1 to 4.10 are accompanied with explanatory tables (Table 1.1 A to 4.10 A) where the numbering and the Affymetrix Id are further defined by other parameters, e.g. gene bank accession number.
  • the inv(3)(q21q26)/t(3;3)(q21;q26) can be found in about 1-2% of all unselected AML and MDS RAEB-1 and RAEB-2. Although these 3q21q26 aberrations are correlated with characteristic features such as thrombocytosis, micromegakaryocytes, trilineage dysplasia, and with an unfavourable prognosis, they are not strictly correlated with an FAB subtype. The breakpoints in 3q21 as well as in 3q26 vary considerably at the molecular level. Long range activation of the EVI1 gene, residing in 3q26, was reported to be involved in the pathogenetic mechanism of these AML.
  • inv(3)/t(3;3) positive AML can be characterized by distinct gene expression patterns as recently demonstrated for other AML with balanced chromosomal aberrations.
  • Distinct expression signatures accurately distinguish the 3q21q26 AML from all other AML subtypes with 100% accuracy, both by supervised and by unsupervised analysis.
  • one of the differentially expressed genes was EVIL
  • Two different microarray probesets revealed absence of EVI1 expression in t(8;21), t(15;17), inv(16), and low or absent expression in normal and complex aberrant karyotypes. High expression was found in t(llq23)/MLL AML and even 4-fold higher in 3q21q26 leukemias.
  • the EVI1 expression was confirmed with a real time LightCycler assay in all 3q21q26 AML and in 205 selected cases of all other groups.
  • the methods section contains both information on statistical analyses used for identification of differentially expressed genes and detailed annotation data of identified microarray probesets.
  • sequence data are omitted due to their large size, and because they do not change, whereas the annotation data are updated periodically, for example new information on chromomal location and functional annotation of the respective gene products. Sequence data are available for download in the NetAffx Download Center (www.affymetrix.com)
  • Microarray probesets for example found to be differentially expressed between different types of leukemia samples are further described by additional information.
  • the fields are of the following types:
  • HG-U133 ProbeSet_ID describes the probe set identifier. Examples are: 200007_at, 20001 l_s_at, 200012_x_at.
  • GeneChip probe array name where the respective probeset is represented. Examples are: Affymetrix Human Genome U133A Array or Affymetrix Human Genome U133B Array.
  • the Sequence Type indicates whether the sequence is an Exemplar, Consensus or Control sequence.
  • An Exemplar is a single nucleotide sequence taken directly from a public database. This sequence could be an mRNA or EST.
  • a Consensus sequence is a nucleotide sequence assembled by Affymetrix, based on one or more sequence taken from a public database.
  • Transcript ID The cluster identification number with a sub-cluster identifier appended.
  • accession number of the single sequence, or representative sequence on which the probe set is based Refer to the "Sequence Source” field to determine the database used.
  • Affymetrix annotational data come from the UniGene record. There is no indication which species-specific databank was used, but some of the possibilities include for example HUGO: The Human Genome Organization. MapLocation:
  • the map location describes the chromosomal location when one is available.
  • Cluster type can be "full length” or “est”, or " — “ if unknown.
  • LocusLink This information represents the LocusLink accession number.
  • the field contains the ID and description for each entry, and there can be multiple entries per probeSet.
  • Example 3 Sample preparation, processing and data analysis
  • Microarray analyses were performed utilizing the GeneChip ® System (Affymetrix, Santa Clara, USA). Hybridization target preparations were performed according to recommended protocols (Affymetrix Technical Manual). In detail, at time of diagnosis, mononuclear cells were purified by FicoU-Hypaque density centrifugation. They had been lysed immediately in RLT buffer (Qiagen, Hilden, Germany), frozen, and stored at -80°C from 1 week to 38 months. For gene expression profiling cell lysates of the leukemia samples were thawed, homogenized (QIAshredder, Qiagen), and total RNA was extracted (RNeasy Mini Kit, Qiagen).
  • RNA isolated from 1 x 10 7 cells was used as starting material for cDNA synthesis with oligo [(dT) 2 T7 ⁇ romotor] 65 primer (cDNA Synthesis System, Roche Applied Science, Mannheim, Germany). cDNA products were purified by phenol/clilorophorm/IAA extraction (Ambion,
  • cRNA was fragmented by alkaline treatment (200 mM Tris-acetate, pH 8.2/500 mM potassium acetate/150 mM magnesium acetate) and added to the hybridization cocktail sufficient for five hybridizations on standard GeneChip microarrays (300 ⁇ l final volume). Washing and staining of the probe arrays was performed according to the recommended Fluidics Station protocol (EukGE-WS2v4).
  • Affymetrix Microarray Suite software version 5.0.1 extracted fluorescence signal intensities from each feature on the microarrays as detected by confocal laser scanning according to the manufacturer's recommendations.
  • Expression analysis quality assessment parameters included visiual array inspection of the scanned image for the presence of image artifacts and correct grid alignment for the identification of distinct probe cells as well as both low 375' ratio of housekeeping controls (mean: 1.90 for GAPDH) and high percentage of detection calls (mean: 46.3% present called genes).
  • the 3' to 5' ratio of GAPDH probesets can be used to assess RNA sample and assay quality. Signal values of the
  • 3' probe sets for GAPDH are compared to the Signal values of the corresponding 5' probe set.
  • the ratio of the 3' probe set to the 5' probe set is generally no more than 3.0.
  • a high 3' to 5' ratio may indicate degraded RNA or inefficient synthesis of ds cDNA or biotinylated cRNA (GeneChip ® Expression Analysis Technical Manual, www.affymetrix.com).
  • Detection calls are used to determine whether the transcript of a gene is detected (present) or undetected (absent) and were calculated using default parameters of the Microarray Analysis Suite MAS 5.0 software package.
  • Bone marrow (BM) aspirates are taken at the time of the initial diagnostic biopsy and remaining material is immediately lysed in RLT buffer (Qiagen), frozen and stored at -80 C until preparation for gene expression analysis.
  • RLT buffer Qiagen
  • RNA extracted RNA extracted from 1 x 107 cells is used as starting material in the subsequent cDNA-Synthesis using Oligo-dT-T7-Promotor Primer (cDNA synthesis Kit, Roche Molecular Biochemicals).
  • the cDNA is purified by phenol-chlorophorm extraction and precipitated with 100% Ethanol over night.
  • biotin-labeled ribonucleotides are incorporated during the in vitro transcription reaction (Enzo® BioArrayTM HighYieldTM RNA Transcript Labeling Kit, ENZO). After quantification of the purified cRNA (RNeasy Mini Kit, Qiagen), 15 ug are fragmented by alkaline treatment (200 mM Tris-acetate, pH 8.2, 500 mM potassium acetate, 150 mM magnesium acetate) and added to the hybridization cocktail sufficient for 5 hybridizations on standard GeneChip microarrays. Before expression profiling Test3 Probe Arrays (Affymetrix) are chosen for monitoring of the integrity of the cRNA.
  • cRNA-cocktails which showed a ratio of the messured intensity of the 3' to the 5' end of the GAPDH gene less than 3.0 are selected for subsequent hybridization on HG-U133 probe arrays (Affymetrix). Washing and staining the Probe arrays is performed as described ( founded Affymetrix-Original- Literatur (LOCKHART und LIPSHUTZ).
  • the Affymetrix software (Microarray Suite, Version 4.0.1) extracted fluorescence intensities from each element on the arrays as detected by confocal laser scanning according to the manufacturers recommendations .
  • OVA One-Versus-AII
  • _s_ a CBFA2T1 -13.48 6.51 E-07 4.00E-04 -1.63 -7.44 8q22 22 212895.
  • _s_ at ABR 3.03 3.97E-07 3.50E-04 1.38 7.38 17p13.3 23 223534.
  • _at PTPN12 2.76 6.85E-07 4.00E-04 1.39 7.29 7q11.23 27 220974.
  • _s_ at ATP1B1 5.21 2.00E-06 7.03E-04 1.50 7.27 1q22-q25 29 201938.
  • CDK2AP1 2.10 7.57E-08 1.28E-04 1.27 7.26 12q24.31 30 207839.

Abstract

Disclosed is a method for distinguishing AML subtype AML_inv(3) from other AML subtypes in a sample by determining the expression level of markers, as well as a diagnostic kit and an apparatus containing the markers.

Description

Method for distinguishing AML subtype inv(3)(q21q26)/t(3;3)(q21q26) from other AML subtypes
The present invention is directed to a method for distinguishing AML subtype inv(3)(q21q26)/t(3;3)(q21q26) (abbreviated: AML_inv(3)) from other AML subtypes, in particular from t(8;21), t(15;17), inv(16), t(l lq23)/MLL (abbreviated: AML_llq23), AML_normal (normal karyotype) and/or AML_CA (complex aberrant karyotype) by determining the expression level of selected marker genes.
Leukemias are classified into four different groups or types: acute myeloid (AML), acute lymphatic (ALL), chronic myeloid (CML) and chronic lymphatic leukemia (CLL). Within these groups, several subcategories can be identified further using a panel of standard techniques as described below. These different subcategories in leukemias are associated with varying clinical outcome and therefore are the basis for different treatment strategies. The importance of highly specific classification may be illustrated in detail further for the AML as a very heterogeneous group of diseases. Effort is aimed at identifying biological entities and to distinguish and classify subgroups of AML which are associated with a favorable, intermediate or unfavorable prognosis, respectively. In 1976, the FAB classification was proposed by the French-American-British co-operative group which was based on cytomorphology and cytochemistry in order to separate AML subgroups according to the morphological appearance of blasts in the blood and bone marrow. In addition, it was recognized that genetic abnormalities occurring in the leukemic blast had a major impact on the morphological picture and even more on the prognosis. So far, the karyotype of the leukemic blasts is the most important independent prognostic factor, regarding response to therapy as well as survival.
Usually, a combination of methods is necessary to obtain the most important information in leukemia diagnostics: Analysis of the morphology and cytochemistry of bone marrow blasts and peripheral blood cells is necessary to establish the diagnosis, hi some cases the addition of immunophenotyping is mandatory to separate very undifferentiated AML from acute lymphoblastic leukemia and CLL. Leukemia subtypes investigated can be diagnosed by cytomorphology alone, only if an expert reviews the smears. However, a genetic analysis based on chromosome analysis, fluorescence in situ hybridization or RT- PCR and immunophenotyping is required in order to assign all cases into the right category. The aim of these techniques besides diagnosis is mainly to determine the prognosis of the leukemia. A major disadvantage of these methods, however, is that viable cells are necessary as the cells for genetic analysis have to divide in vitro in order to obtain metaphases for the analysis. Another problem is the long time of 72 hours from receipt of the material in the laboratory to obtain the result. Furthermore, great experience in preparation of chromosomes and even more in analyzing the karyotypes is required to obtain the correct result in at least 90% of cases. Using these techniques in combination, hematological malignancies in a first approach are separated into chronic myeloid leukemia (CML), chronic lymphatic
(CLL), acute lymphoblastic (ALL), and acute myeloid leukemia (AML). Within the latter three disease entities several prognostically relevant subtypes have been established. As a second approach this further sub-classification is based mainly on genetic abnormalities of the leukemic blasts and clearly is associated with different prognoses.
The sub-classification of leukemias becomes increasingly important to guide therapy. The development of new, specific drugs and treatment approaches requires the identification of specific subtypes that may benefit from a distinct therapeutic protocol and, thus, can improve outcome of distinct subsets of leukemia. For example, the new therapeutic drug (STI571, Imatinib) inhibits the CML specific chimeric tyrosine kinase BCR-ABL generated from the genetic defect observed in CML, the BCR-ABL-rearrangement due to the translocation between chromosomes 9 and 22 (t(9;22) (q34; qll)). In patients treated with this new drug, the therapy response is dramatically higher as compared to all other drugs that had been used so far. Another example is the subtype of acute myeloid leukemia AML M3 and its variant M3v both with karyotype t[15;17)(q22; ql l-12). The introduction of a new drug (all-trans retinoic acid - ATRA) has improved the outcome in this subgroup of patient from about 50% to 85 % long-term survivors. As it is mandatory for these patients suffering from these specific leukemia subtypes to be identified as fast as possible so that the best therapy can be applied, diagnostics today must accomplish sub-classification with maximal precision. Not only for these subtypes but also for several other leukemia subtypes different treatment approaches could improve outcome. Therefore, rapid and precise identification of distinct leukemia subtypes is the future goal for diagnostics. Thus, the technical problem underlying the present invention was to provide means for leukemia diagnostics which overcome at least some of the disadvantages of the prior art diagnostic methods, in particular encompassing the time-consuming and unreliable combination of different methods and which provides a rapid assay to unambiguously distinguish one AML subtype from another, e.g. by genetic analysis.
According to Golub et al. (Science, 1999, 286, 531-7), gene expression profiles can be used for class prediction and discriminating AML from ALL samples. However, for the analysis of acute leukemias the selection of the two different subgroups was performed using exclusively morphologic-phenotypical criteria. This was only descriptive and does not provide deeper insights into the pathogenesis or the underlying biology of the leukemia. The approach reproduces only very basic knowledge of cytomorphology and intends to differentiate classes. The data is not sufficient to predict prognostically relevant cytogenetic aberrations.
Furthermore, the international application WO-A 03/039443 discloses marker genes the expression levels of which are characteristic for certain leukemia, e.g. AML subtypes and additionally discloses methods for differentiating between the subtype of AML cells by determining the expression profile of the disclosed marker genes. However, WO-A 03/039443 does not provide guidance which set of distinct genes discriminate between two subtypes and, as such, can be routineously taken in order to distinguish one AML subtype from another.
The problem is solved by the present invention, which provides a method for distinguishing AML subtype AML_inv(3) from other AML subtypes in a sample, the method comprising determining the expression level of markers selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4, wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.1 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.1 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.2 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.2 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.3 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.3 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.4 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.4 having a positive fc value, is indicative for the presence of AML_normal when AML_normal is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.5 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.5 having a positive fc value, is indicative for the presence of AML_t(15;17) when AML_t(15;17) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.6 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.6 having a positive fc value, is indicative for the presence of AML_t(8 ;21 ) when AML_t(8 ;21 ) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.1 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.1 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_inv(16), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.2 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.2 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_inv(3), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.3 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.3 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_normal, and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.4 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.4 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_t(15;17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.5 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.5 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_t(8;21), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.6 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.6 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML_inv(3), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.7 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.7 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML_normal, and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.8 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.8 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML_t(15;17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.9 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.9 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML_t(8;21), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.10 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.10 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from AML_normal, and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.11 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.11 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from AML_t(15;17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.12 having a negative fc value, and or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.12 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from AML_t(8;21), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.13 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.13 having a positive fc value, is indicative for the presence of AML_normal when AML_normal is distinguished from AML_t(15;17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.14 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.14 having a positive fc value, is indicative for the presence of AML_normal when AML_normal is distinguished from AML_t(8;21), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.15 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.15 having a positive fc value, is indicative for the presence of AML_t(15;17) when AML_t(15;17) is distinguished from AML_t(8;21 ), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.1 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.1 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.2 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.2 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.3 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.3 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.4 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.4 having a positive fc value, is indicative for the presence of AML_t(15;17) when AML_t(15;17) i is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.5 having a negative fc value, aanndd//or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.5 having a positive fc value, is indicative for the presence of AML_t(8;21) when AML_t(8;21) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.1 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.1 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_inv(16), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.2 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.2 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_inv(3), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.3 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.3 having a positive fc value, is indicative for the presence of AML_11 q23 when AML_11 q23 is distinguished from AML_t(15;17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.4 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.4 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_t(8;21), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.5 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.5 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML_inv(3), and or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.6 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.6 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML_t(15;17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.7 having a negative fc value, and or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.7 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML__t(8;21), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.8 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.8 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from AML_t( 15 ; 17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.9 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.9 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from AML_t(8;21), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.10 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.10 having a positive fc value, is indicative for the presence of AML_t(15;17)when AML_t(15;17)is distinguished from AML_t(8;21).
It has to be noted for clarification, that the data of Tables 1 and 2 consider the determination of AML with normal karyotype (AMLjnormal), whereas the data of Tables 3 and 4 do not consider the determination of AML with normal karyotype. As a consequence, a different gene expression profile between the analysis of Table 1/2 and 3/4 can be reflected.
As used herein, the following definitions apply to the above abbreviations:
AML_inv(3): AML with inversion 3
AML_t(8;21): AML with t(8;21) translocation AML_t(15;17): AML with t(15;17) translocation
AML_inv(16): AML with inversion 16
AML_l lq23: t(llq23)/MLL, AML with t(llq23) translocation on the mixed lineage leukaemia gene (MLL)
AMLjtiormal: AML with normal karytype.
As used herein, "all other subtypes" refer to the subtypes of the present invention, the one which is under investigation versus the all others being included in the present invention.
According to the present invention, a "sample" means any biological material containing genetic information in the form of nucleic acids or proteins obtainable or obtained from an individual. The sample includes e.g. tissue samples, cell samples, bone marrow and/or body fluids such as blood, saliva, semen. Preferably, the sample is blood or bone marrow, more preferably the sample is bone marrow. The person skilled in the art is aware of methods, how to isolate nucleic acids and proteins from a sample. A general method for isolating and preparing nucleic acids from a sample is outlined in Example 3.
According to the present invention, the term "lower expression" is generally assigned to all by numbers and Affymetrix Identification Numbers (ID), definable polynucleotides the t-values and fold change (fc) values of which are negative, as indicated in the Tables. Accordingly, the term "higher expression" is generally assigned to all by numbers and Affymetrix Id. definable polynucleotides the t- values and fold change (fc) values of which are positive.
According to the present invention, the term "expression" refers to the process by which mRNA or a polypeptide is produced based on the nucleic acid sequence of a gene, i.e. „expression" also includes the formation of mRNA upon transcription. In accordance with the present invention, the term „determining the expression level" preferably refers to the determination of the level of expression, namely of the markers.
Generally, "marker" refers to any genetically controlled difference which can be used in the genetic analysis of a test versus a control sample, for the purpose of assigning the sample to a defined genotype or phenotype. As used herein,
"markers" refer to genes which are differentially expressed in, e.g., different AML subtypes. The markers can be defined by their gene symbol name, their encoded protein name, their transcript identification number (cluster identification number), the data base accession number, public accession number or GenBank identifier or, as done in the present invention, Affymetrix identification number, chromosomal location, UniGene accession number and cluster type, LocusLink accession number (see Examples and Tables).
The Affymetrix identification number (affy id) is accessible for anyone and the person skilled in the art by entering the "gene expression omnibus" internet page of the National Center for Biotechnology Information (NCBI) (http://www.ncbi.nlm.nih.gov/geo/). In particular, the affy id's of the polynucleotides used for the method of the present invention are derived from the so-called U133 chip. The sequence data of each identification number can be viewed at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL96
Generally, the expression level of a marker is determined by the determining the expression of its corresponding "polynucleotide" as described hereinafter.
According to the present invention, the term „polynucleotide" refers, generally, to a DNA, in particular cDNA, or RNA, in particular a cRNA, or a portion thereof or a polypeptide or a portion thereof. In the case of RNA (or cDNA), the polynucleotide is formed upon transcription of a nucleotide sequence which is capable of expression. The polynucleotide fragments refer to fragments preferably of between at least 8, such as 10, 12, 15 or 18 nucleotides and at least 50, such as 60, 80, 100, 200 or 300 nucleotides in length, or a complementary sequence thereto, representing a consecutive stretch of nucleotides of a gene, cDNA or mRNA. In other terms, polynucleotides include also any fragment (or complementary sequence thereto) of a sequence derived from any of the markers defined above as long as these fragments unambiguously identify the marker.
The determination of the expression level may be effected at the transcriptional or translational level, i.e. at the level of mRNA or at the protein level. Protein fragments such as peptides or polypeptides advantageously comprise between at least 6 and at least 25, such as 30, 40, 80, 100 or 200 consecutive amino acids representative of the corresponding full length protein. Six amino acids are generally recognized as the lowest peptidic stretch giving rise to a linear epitope recognized by an antibody, fragment or derivative thereof. Alternatively, the proteins or fragments thereof may be analysed using nucleic acid molecules specifically binding to three-dimensional structures (aptamers).
Depending on the nature of the polynucleotide or polypeptide, the determination of the expression levels may be effected by a variety of methods. For determining and detecting the expression level, it is preferred in the present invention that the polynucleotide, in particular the cRNA, is labelled. The labelling of the polynucleotide or a polypeptide can occur by a variety of methods known to the skilled artisan. The label can be fluorescent, chemiluminescent, bioluminescent, radioactive (such as 3H or 32P). The labelling compound can be any labelling compound being suitable for the labelling of polynucleotides and/or polypeptides. Examples include fluorescent dyes, such as fluorescein, dichlorofluorescein, hexachlorofluorescein, BODIPY variants, ROX, tetramethylrhodamin, rhodamin X, Cyanine-2, Cyanine-3, Cyanine-5, Cyanine-7, IRD40, FluorX, Oregon Green, Alexa variants (available e.g. from Molecular Probes or Amersham Biosciences) and the like, biotin or biotinylated nucleotides, digoxigenin, radioisotopes, antibodies, enzymes and receptors. Depending on the type of labelling, the detection is done via fluorescence measurements, conjugation to streptavidin and/or avidin, antigen-antibody- and/or antibody-antibody- interactions, radioactivity measurements, as well as catalytic and/or receptor/ligand interactions. Suitable methods include the direct labelling (incorporation) method, the amino-modified (amino-allyl) nucleotide method (available e.g. from Ambion), and the primer tagging method (DNA dendrimer labelling, as kit available e.g. from Genisphere). Particularly preferred for the present invention is the use of biotin or biotinylated nucleotides for labelling, with the latter being directly incorporated into, e.g. the cRNA polynucleotide by in vitro transcription.
If the polynucleotide is mRNA, cDNA may be prepared into which a detectable label, as exemplified above, is incorporated. Said detectably labelled cDNA, in single-stranded form, may then be hybridised, preferably under stringent or highly stringent conditions to a panel of single-stranded oligonucleotides representing different genes and affixed to a solid support such as a chip. Upon applying appropriate washing steps, those cDNAs will be detected or quantitatively detected that have a counterpart in the oligonucleotide panel. Various advantageous embodiments of this general method are feasible. For example, the mRNA or the cDNA may be amplified e.g. by polymerase chain reaction, wherein it is preferable, for quantitative assessments, that the number of amplified copies corresponds relative to further amplified mRNAs or cDNAs to the number of mRNAs originally present in the cell. In a preferred embodiment of the present invention, the cDNAs are transcribed into cRNAs prior to the hybridisation step wherein only in the transcription step a label is incorporated into the nucleic acid and wherein the cRNA is employed for hybridisation. Alternatively, the label may be attached subsequent to the transcription step. Similarly, proteins from a cell or tissue under investigation may be contacted with a panel of aptamers or of antibodies or fragments or derivatives thereof. The antibodies etc. may be affixed to a solid support such as a chip. Binding of proteins indicative of an AML subtype may be verified by binding to a detectably labelled secondary antibody or aptamer. For the labelling of antibodies, it is referred to Harlow and Lane, "Antibodies, a laboratory manual", CSH Press, 1988, Cold Spring Harbor. Specifically, a minimum set of proteins necessary for diagnosis of all AML subtypes may be selected for creation of a protein array system to make diagnosis on a protein lysate of a diagnostic bone marrow sample directly. Protein
Array Systems for the detection of specific protein expression profiles already are available (for example: Bio-Plex, BIORAD, Mϋnchen, Germany). For this application preferably antibodies against the proteins have to be produced and immobilized on a platform e.g. glasslides or microtiterplates. The immobilized antibodies can be labelled with a reactant specific for the certain target proteins as discussed above. The reactants can include enzyme substrates, DNA, receptors, antigens or antibodies to create for example a capture sandwich immunoassay.
For reliably distinguishing AML subtypes it is useful that the expression of more than one of the above defined markers is determined. As a criterion for the choice of markers, the statistical significance of markers as expressed in q or p values based on the concept of the false discovery rate is determined. In doing so, a measure of statistical significance called the q value is associated with each tested feature. The q value is similar to the p value, except it is a measure of significance in terms of the false discovery rate rather than the false positive rate (Storey JD and
Tibshirani R. Proc.Natl.Acad.Sci., 2003, Vol. 100:9440-5).
In a preferred embodiment of the present invention, markers as defined in Tables 1- 4 having a q- value of less than 3E-06, more preferred less than 1.5E-09, most preferred less than 1.5E-11, less than 1.5E-20, less than 1.5E-30, are measured.
Of the above defined markers, the expression level of at least two, preferably of at least ten, more preferably of at least 25, most preferably of 50 of at least one of the Tables of the markers is determined. In another preferred embodiment, the expression level of at least 2, of at least 5, of at least 10 out of the markers having the numbers 1 - 10, 1-20, 1-40, 1-50 of at least one of the Tables are measured.
The level of the expression of the „marker", i.e. the expression of the polynucleotide is indicative of the AML subtype of a cell or an organism. The level of expression of a marker or group of markers is measured and is compared with the level of expression of the same marker or the same group of markers from other cells or samples. The comparison may be effected in an actual experiment or in silico. When the expression level also referred to as expression pattern or expression signature (expression profile) is measurably different, there is according to the invention a meaningful difference in the level of expression. Preferably the difference at least is 5 %, 10% or 20%, more preferred at least 50% or may even be as high as 75% or 100%. More preferred the difference in the level of expression is at least 200%, i.e. two fold, at least 500%, i.e. five fold, or at least 1000%, i.e. 10 fold.
Accordingly, the expression level of markers expressed lower in a first subtype than in at least one second subtype, which differs from the first subtype, is at least 5 %, 10% or 20%, more preferred at least 50% or may even be 75% or 100%, i.e.
2-fold lower, preferably at least 10-fold, more preferably at least 50- fold, and most preferably at least 100-fold lower in the first subtype. On the other hand, the expression level of markers expressed higher in a first subtype than in at least one second subtype, which differs from the first subtype, is at least 5 %, 10% or 20%, more preferred at least 50% or may even be 75% or 100%, i.e. 2-fold higher, preferably at least 10-fold, more preferably at least 50-fold, and most preferably at least 100-fold higher in the first subtype.
In another embodiment of the present invention, the sample is derived from an individual having leukaemia, preferably AML.
For the method of the present invention it is preferred if the polynucleotide the expression level of which is determined is in form of a transcribed polynucleotide. A particularly preferred transcribed polynucleotide is an mRNA, a cDNA and/or a cRNA, with the latter being preferred. Transcribed polynucleotides are isolated from a sample, reverse transcribed and/or amplified, and labelled, by employing methods well-known the person skilled in the art (see Example 3). In a preferred embodiment of the methods according to the invention, the step of determining the expression profile further comprises amplifying the transcribed polynucleotide.
In order to determine the expression level of the transcribed polynucleotide by the method of the present invention, it is preferred that the method comprises hybridizing the transcribed polynucleotide to a complementary polynucleotide, or a portion thereof, under stringent hybridization conditions, as described hereinafter.
The term "hybridizing" means hybridization under conventional hybridization conditions, preferably under stringent conditions as described, for example, in Sambrook, J., et al, in "Molecular Cloning: A Laboratory Manual" (1989), Eds. J. Sambrook, E. F. Fritsch and T. Maniatis, Cold Spring Harbour Laboratory Press, Cold Spring Harbour, NY and the further definitions provided above. Such conditions are, for example, hybridization in 6x SSC, pH 7.0 / 0.1% SDS at about
45°C for 18-23 hours, followed by a washing step with 2x SSC/0.1% SDS at 50°C. In order to select the stringency, the salt concentration in the washing step can for example be chosen between 2x SSC/0.1% SDS at room temperature for low stringency and 0.2x SSC/0.1% SDS at 50°C for high stringency. In addition, the temperature of the washing step can be varied between room temperature, ca. 22°C, for low stringency, and 65 °C to 70° C for high stringency. Also contemplated are polynucleotides that hybridize at lower stringency hybridization conditions. Changes in the stringency of hybridization and signal detection are primarily accomplished through the manipulation, preferably of formamide concentration (lower percentages of formamide result in lowered stringency), salt conditions, or temperature. For example, lower stringency conditions include an overnight incubation at 37°C in a solution comprising 6X SSPE (20X SSPE = 3M NaCl; 0.2M NaH2PO4; 0.02M EDTA, pH 7.4), 0.5% SDS, 30% formamide, 100 mg/ml salmon sperm blocking DNA, followed by washes at 50°C with 1 X SSPE, 0.1 % SDS. In addition, to achieve even lower stringency, washes performed following stringent hybridization can be done at higher salt concentrations (e.g. 5x SSC). Variations in the above conditions may be accomplished through the inclusion and/or substitution of alternate blocking reagents used to suppress background in hybridization experiments. The inclusion of specific blocking reagents may require modification of the hybridization conditions described above, due to problems with compatibility. "Complementary" and "complementarity", respectively, can be described by the percentage, i.e. proportion, of nucleotides which can form base pairs between two polynucleotide strands or within a specific region or domain of the two strands. Generally, complementary nucleotides are, according to the base pairing rules, adenine and thymine (or adenine and uracil), and cytosine and guanine. Complementarity may be partial, in which only some of the nucleic acids' bases are matched according to the base pairing rules. Or, there may be a complete or total complementarity between the nucleic acids. The degree of complementarity between nucleic acid strands has effects on the efficiency and strength of hybridization between nucleic acid strands.
Two nucleic acid strands are considered to be 100% complementary to each other over a defined length if in a defined region all adenines of a first strand can pair with a thymine (or an uracil) of a second strand, all guanines of a first strand can pair with a cytosine of a second strand, all thymine (or uracils) of a first strand can pair with an adenine of a second strand, and all cytosines of a first strand can pair with a guanine of a second strand, and vice versa. According to the present invention, the degree of complementarity is determined over a stretch of 20, preferably 25, nucleotides, i.e. a 60% complementarity means that within a region of 20 nucleotides of two nucleic acid strands 12 nucleotides of the first strand can base pair with 12 nucleotides of the second strand according to the above ruling, either as a stretch of 12 contiguous nucleotides or interspersed by non-pairing nucleotides, when the two strands are attached to each other over said region of 20 nucleotides. The degree of complementarity can range from at least about 50% to full, i.e. 100% complementarity. Two single nucleic acid strands are said to be "substantially complementary" when they are at least about 80% complementary, preferably about 90% or higher. For carrying out the method of the present invention substantial complementarity is preferred.
Preferred methods for detection and quantification of the amount of polynucleotides, i.e. for the methods according to the invention allowing the determination of the level of expression of a marker, are those described by Sambrook et al. (1989) or real time methods known in the art as the TaqMan® method disclosed in WO92/02638 and the corresponding U.S. 5,210,015, U.S.
5,804,375, U.S. 5,487,972. This method exploits the exonuclease activity of a polymerase to generate a signal. In detail, the (at least one) target nucleic acid component is detected by a process comprising contacting the sample with an oligonucleotide containing a sequence complementary to a region of the target nucleic acid component and a labeled oligonucleotide containing a sequence complementary to a second region of the same target nucleic acid component sequence strand, but not including the nucleic acid sequence defined by the first oligonucleotide, to create a mixture of duplexes during hybridization conditions, wherein the duplexes comprise the target nucleic acid annealed to the first oligonucleotide and to the labeled oligonucleotide such that the 3 '-end of the first oligonucleotide is adjacent to the 5 '-end of the labeled oligonucleotide. Then this mixture is treated with a template-dependent nucleic acid polymerase having a 5' to 3' nuclease activity under conditions sufficient to permit the 5' to 3' nuclease activity of the polymerase to cleave the annealed, labeled oligonucleotide and release labeled fragments. The signal generated by the hydrolysis of the labeled oligonucleotide is detected and/ or measured. TaqMan® technology eliminates the need for a solid phase bound reaction complex to be formed and made detectable.
Other methods include e.g. fluorescence resonance energy transfer between two adjacently hybridized probes as used in the LightCycler® format described in U.S. 6,174,670.
A preferred protocol if the marker, i.e. the polynucleotide, is in form of a transcribed nucleotide, is described in Example 3, where total RNA is isolated, cDNA and, subsequently, cRNA is synthesized and biotin is incorporated during the transcription reaction. The purified cRNA is applied to commercially available arrays which can be obtained e.g. from Affymetrix. The hybridized cRNA is detected according to the methods described in Example 3. The arrays are produced by photolithography or other methods known to experts skilled in the art e.g. from U.S. 5,445,934, U.S. 5,744,305, U.S. 5,700,637, U.S. 5,945,334 and EP 0 619 321 or EP 0 373 203, or as decribed hereinafter in greater detail.
In another embodiment of the present invention, the polynucleotide or at least one of the polynucleotides is in form of a polypeptide. In another preferred embodiment, the expression level of the polynucleotides or polypeptides is detected using a compound which specifically binds to the polynucleotide of the polypeptide of the present invention. As used herein, "specifically binding" means that the compound is capable of discriminating between two or more polynucleotides or polypeptides, i.e. it binds to the desired polynucleotide or polypeptide, but essentially does not bind unspecifically to a different polynucleotide or polypeptide.
The compound can be an antibody, or a fragment thereof, an enzyme, a so-called small molecule compound, a protein-scaffold, preferably an anticalin. In a preferred embodiment, the compound specifically binding to the polynucleotide or polypeptide is an antibody, or a fragment thereof.
As used herein, an "antibody" comprises monoclonal antibodies as first described by Kohler and Milstein in Nature 278 (1975), 495-497 as well as polyclonal antibodies, i.e. antibodies contained in a polyclonal antiserum. Monoclonal antibodies include those produced by transgenic mice. Fragments of antibodies include F(ab') , Fab and Fv fragments. Derivatives of antibodies include scFvs, chimeric and humanized antibodies. See, for example Harlow and Lane, loc. cit. For the detection of polypeptides using antibodies or fragments thereof, the person skilled in the art is aware of a variety of methods, all of which are included in the present invention. Examples include immunoprecipitation, Western blotting, Enzyme-linked immuno sorbent assay (ELISA), Enzyme-linked immuno sorbent assay (RIA), dissociation-enhanced lanthanide fluoro immuno assay (DELFIA), scintillation proximity assay (SPA). For detection, it is desirable if the antibody is labelled by one of the labelling compounds and methods described supra.
In another preferred embodiment of the present invention, the method for distinguishing AML subtype AML_inv(3) from other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(l lq23)/MLL, and/or AML_normal is carried out on an array.
In general, an "array" or "microarray" refers to a linear or two- or three dimensional arrangement of preferably discrete nucleic acid or polypeptide probes which comprises an intentionally created collection of nucleic acid or polypeptide probes of any length spotted onto a substrate/solid support. The person skilled in the art knows a collection of nucleic acids or polypeptide spotted onto a substrate/solid support also under the term "array". As known to the person skilled in the art, a microarray usually refers to a miniaturised array arrangement, with the probes being attached to a density of at least about 10, 20, 50, 100 nucleic acid molecules referring to different or the same genes per cm2. Furthermore, where appropriate an array can be referred to as "gene chip". The array itself can have different formats, e.g. libraries of soluble probes or libraries of probes tethered to resin beads, silica chips, or other solid supports.
The process of array fabrication is well-known to the person skilled in the art. In the following, the process for preparing a nucleic acid array is described. Commonly, the process comprises preparing a glass (or other) slide (e.g. chemical treatment of the glass to enhance binding of the nucleic acid probes to the glass surface), obtaining DNA sequences representing genes of a genome of interest, and spotting sequences these sequences of interest onto glass slide. Sequences of interest can be obtained via creating a cDNA library from an mRNA source or by using publicly available databases, such as GeneBank, to annotate the sequence information of custom cDNA libraries or to identify cDNA clones from previously prepared libraries. Generally, it is recommendable to amplify obtained sequences by PCR in order to have sufficient amounts of DNA to print on the array. The liquid containing the amplified probes can be deposited on the array by using a set of microspotting pins. Ideally, the amount deposited should be uniform. The process can further include UV-crosslinking in order to enhance immobilization of the probes on the array.
In a preferred embodiment, the array is a high density oligonucleotide (oligo) array using a light-directed chemical synthesis process, employing the so-called photolithography technology. Unlike common cDNA arrays, oligo arrays
(according to the Affymetrix technology) use a single-dye technology. Given the sequence information of the markers, the sequence can be synthesized directly onto the array, thus, bypassing the need for physical intermediates, such as PCR products, required for making cDNA arrays. For this purpose, the marker, or partial sequences thereof, can be represented by 14 to 20 features, preferably by less than
14 features, more preferably less than 10 features, even more preferably by 6 features or less, with each feature being a short sequence of nucleotides
(oligonucleotide), which is a perfect match (PM) to a segment of the respective gene. The PM oligonucleotide are paired with mismatch (MM) oligonucleotides which have a single mismatch at the central base of the nucleotide and are used as
"controls". The chip exposure sites are defined by masks and are deprotected by the use of light, followed by a chemical coupling step resulting in the synthesis of one nucleotide. The masking, light deprotection, and coupling process can then be repeated to synthesize the next nucleotide, until the nucleotide chain is of the specified length.
Advantageously, the method of the present invention is carried out in a robotics system including robotic plating and a robotic liquid transfer system, e.g. using microfluidics, i.e. channelled structured.
A particular preferred method according to the present invention is as follows:
1. Obtaining a sample, e.g. bone marrow aliquots, from a patient having AML
2. Extracting RNA, preferably mRNA, from the sample
3. Reverse transcribing the RNA into cDNA
4. In vitro transcribing the cDNA into cRNA 5. Fragmenting the cRNA
6. Hybridizing the fragmented cRNA on standard microarrays
7. Determining hybridization
In another embodiment, the present invention is directed to the use of at least one marker selected from the markers identifiable by their Affymetrix Identification
Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4, for the manufacturing of a diagnostic for distinguishing AML subtype AML_inv(3) from other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(l lq23)/MLL, and/or AML_normal. The use of the present invention is particularly advantageous for distinguishing AML subtype AML_inv(3) from other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(l lq23)/MLL, and/or AML_normal in an individual having AML. The use of said markers for diagnosis of WHO classified leukemia subtypes, preferably based on microarray technology, offers the following advantages: (1) more rapid and more precise diagnosis, (2) easy to use in laboratories without specialized experience, (3) abolishes the requirement for analyzing viable cells for chromosome analysis (transport problem), and (4) very experienced hematologists for cytomorphology and cytochemistry, immunophenotyping as well as cytogeneticists and molecularbiologists are no longer required.
Accordingly, the present invention refers to a diagnostic kit containing at least one marker selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4, for distinguishing AML subtype AML_inv(3) from other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(l lq23)/MLL, and/or AML_normal, in combination with suitable auxiliaries. Suitable auxiliaries, as used herein, include buffers, enzymes, labelling compounds, and the like. In a preferred embodiment, the marker contained in the kit is a nucleic acid molecule which is capable of hybridizing to the mRNA corresponding to at least one marker of the present invention. Preferably, the at least one nucleic acid molecule is attached to a solid support, e.g. a polystyrene microtiter dish, nitrocellulose membrane, glass surface or to non-immobilized particles in solution.
In another preferred embodiment, the diagnostic kit contains at least one reference for an AML subtype AML_inv(3) and/or any other AML subtype, preferably from t(8;21), t(15;17), inv(16), t(llq23)/MLL, and/or AML_normal. As used herein, the reference can be a sample or a data bank.
In another embodiment, the present invention is directed to an apparatus for distinguishing AML subtype AML_inv(3) from other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(l lq23)/MLL, and/or AML_normal in a sample, containing a reference data bank obtainable by comprising (a) compiling a gene expression profile of a patient sample by determining the expression level at least one marker selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4 and (b) classifying the gene expression profile by means of a machine learning algorithm.
According to the present invention, the "machine learning algorithm" is a computational-based prediction methodology, also known to the person skilled in the art as "classifier", employed for characterizing a gene expression profile. The signals corresponding to a certain expression level which are obtained by the microarray hybridization are subjected to the algorithm in order to classify the expression profile. Supervised learning involves "training" a classifier to recognize the distinctions among classes and then "testing" the accuracy of the classifier on an independent test set. For new, unknown samples the classifier shall predict into which class the sample belongs. Preferably, the machine learning algorithm is selected from the group consisting of Weighted Voting, K-Nearest Neighbors, Decision Tree Induction, Support Vector Machines (SVM), and Feed-Forward Neural Networks. Most preferably, the machine learning algorithm is Support Vector Machine, such as polynomial kernel and Gaussian Radial Basis Function-kernel SVM models.
The classification accuracy of a given gene list for a set of microarray experiments is preferably estimated using Support Vector Machines (SVM), because there is evidence that SVM-based prediction slightly outperforms other classification techniques like k-Nearest Neighbors (k-NN). The LIB SVM software package version 2.36 was used (SVM-type: C-SVC, linear kernel (http://www.csie.nm.edu.tw/~cjlin/libsvm )). The skilled artisan is furthermore referred to Brown et al., Proc.Natl.Acad.Sci., 2000; 97: 262-267, Furey et al, Bioinformatics. 2000; 16: 906-914, and Vapnik V. Statistical Learning Theory. New York: Wiley, 1998.
In detail, the classification accuracy of a given gene list for a set of microarray experiments can be estimated using Support Vector Machines (SVM) as supervised learning technique. Generally, SVMs are trained using differentially expressed genes which were identified on a subset of the data and then this trained model is employed to assign new samples to those trained groups from a second and different data set. Differentially expressed genes were identified applying ANOVA and t-test-statistics (Welch t-test). Based on identified distinct gene expression signatures respective training sets consisting of 2/3 of cases and test sets with 1/3 of cases to assess classification accuracies are designated. Assignment of cases to training and test set is randomized and balanced by diagnosis. Based on the training set a Support Vector Machine (SVM) model is built.
According to the present invention, the apparent accuracy, i.e. the overall rate of correct predictions of the complete data set was estimated by lOfold cross validation. This means that the data set was divided into 10 approximately equally sized subsets, an SVM-model was trained for 9 subsets and predictions were generated for the remaining subset. This training and prediction process was repeated 10 times to include predictions for each subset. Subsequently the data set was split into a training set, consisting of two thirds of the samples, and a test set with the remaining one third. Apparent accuracy for the training set was estimated by lOfold cross validation (analogous to apparent accuracy for complete set). A SVM-model of the training set was built to predict diagnosis in the independent test set, thereby estimating true accuracy of the prediction model. This prediction approach was applied both for overall classification (multi-class) and binary classification (diagnosis X => yes or no). For the latter, sensitivity and specificity were calculated:
Sensitivity = (number of positive samples predicted)/(number of true positives)
Specificity = (number of negative samples predicted)/(number of true negatives)
In a preferred embodiment, the reference data bank is backed up on a computational data memory chip which can be inserted in as well as removed from the apparatus of the present invention, e.g. like an interchangeable module, in order to use another data memory chip containing a different reference data bank.
The apparatus of the present invention containing a desired reference data bank can be used in a way such that an unknown sample is, first, subjected to gene expression profiling, e.g. by microarray analysis in a manner as described supra or in the art, and the expression level data obtained by the analysis are, second, fed into the apparatus and compared with the data of the reference data bank obtainable by the above method. For this purpose, the apparatus suitably contains a device for entering the expression level of the data, for example a control panel such as a keyboard. The results, whether and how the data of the unknown sample fit into the reference data bank can be made visible on a provided monitor or display screen and, if desired, printed out on an incorporated of connected printer.
Alternatively, the apparatus of the present invention is equipped with particular appliances suitable for detecting and measuring the expression profile data and, subsequently, proceeding with the comparison with the reference data bank. In this embodiment, the apparatus of the present invention can contain a gripper arm and/or a tray which takes up the microarray containing the hybridized nucleic acids.
In another embodiment, the present invention refers to a reference data bank for distinguishing AML subtype AML_inv(3) from other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(llq23)/MLL, and/or AMLjtiormal in a sample obtainable by comprising (a) compiling a gene expression profile of a patient sample by determining the expression level of at least one marker selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4, and (b) classifying the gene expression profile by means of a machine learning algorithm.
Preferably, the reference data bank is backed up and/or contained in a computational memory data chip.
The invention is further illustrated in the following table and examples, without limiting the scope of the invention:
TABLES 1.1-4.10
Tables 1.1-4.10 show AML subtype analysis of AML subtype AML_inv(3) and other AML subtypes, preferably from t(8;21), t(15;17), inv(16), t(llq23)/MLL, and/or AML_normal. The analysed markers are ordered according to their q- values, beginning with the lowest q-values. For convenience and a better understanding, Tables 1.1 to 4.10 are accompanied with explanatory tables (Table 1.1 A to 4.10 A) where the numbering and the Affymetrix Id are further defined by other parameters, e.g. gene bank accession number.
EXAMPLES
Example 1 : General experimental design of the invention and results
The inv(3)(q21q26)/t(3;3)(q21;q26) can be found in about 1-2% of all unselected AML and MDS RAEB-1 and RAEB-2. Although these 3q21q26 aberrations are correlated with characteristic features such as thrombocytosis, micromegakaryocytes, trilineage dysplasia, and with an unfavourable prognosis, they are not strictly correlated with an FAB subtype. The breakpoints in 3q21 as well as in 3q26 vary considerably at the molecular level. Long range activation of the EVI1 gene, residing in 3q26, was reported to be involved in the pathogenetic mechanism of these AML. However, the pathophysiologic mechanisms of the 3q21q26 leukemia are poorly understood. Here we addressed the question, whether inv(3)/t(3;3) positive AML can be characterized by distinct gene expression patterns as recently demonstrated for other AML with balanced chromosomal aberrations. Fifteen cases with 3q21q26 were hybridized onto the U133 set microarrays (Affymetrix) and compared to a cohort of 97 AML with other balanced chromosomal aberrations: t(8;21) (n=19), t(15;17) (n=20), inv(16) (n=24), t(l lq23)/MLL (n=31), 132 AML with normal and 36 with complex aberrant karyotype. Distinct expression signatures accurately distinguish the 3q21q26 AML from all other AML subtypes with 100% accuracy, both by supervised and by unsupervised analysis. In fact, one of the differentially expressed genes was EVIL Two different microarray probesets revealed absence of EVI1 expression in t(8;21), t(15;17), inv(16), and low or absent expression in normal and complex aberrant karyotypes. High expression was found in t(llq23)/MLL AML and even 4-fold higher in 3q21q26 leukemias. The EVI1 expression was confirmed with a real time LightCycler assay in all 3q21q26 AML and in 205 selected cases of all other groups. Both platforms reproducibly reveal a high correlation of EVI1 expression for both probesets (r=0.943 and r=0.767, respectively). The characteristic immunophenotype of 3q21q26 with high CD34+, low CD97+, low lactotransferrin+, and low MPO+ in comparison to all other subtypes could also be confirmed at the gene expression level. We then focussed on genes known to be involved in megakaryopoiesis. A higher expression of GATA1, GAT A3, HOXC4, some genes for GP-proteins (GP1BA, GP1BB, GP5, and GP6) and IGHM was found in 3q21q26 leukemias but not in other AML. In addition, a high expression of PF4 (platelet factor 4) and its transactivator PBX2 was detected. Expression of TPO was not changed, but its receptor MPL was 6 fold upregulated in 3q21q26 AML in comparison to other AML. Moreover, upregulation of genes known to be targeted by mutations in some inborn platelet disorders were found: ETS1, FLU, WAS, CBFA2T2 and CBFA2T3. As EVI1 was activated by a long range effect in 3q21q26 AML we further investigated genes located in the respective breakpoint regions. In fact many of them were dysregulated in comparison to other AML and normal bone marrow. For example in i) 3q21 high: MYLK, ITGB5, TRAD,
MCM2, TM4SF1, ATP2C1, NCK1, WDR5B ii) 3q21 low: CSTA, SELB, WDR10 iii) 3q26 high: GOLPH4, PDCD10, KCNMB3 iv) 3q26 low: PLD1, FAD104. Thus, like EVI1 many genes in 3q21 and 3q26 may be affected by the 3q21q26 rearrangement, i.e. by long distance effect. In conclusion, the identification of new candidate genes associated with this subtype allows a better understanding of the pathogenesis of the 3q21q26 AML. The specific expression signature together with phenotypic characteristics showed that 3q21q26 AML is a biologically distinct subgroup. As such we suggest to add this subgroup to the WHO classification as an own entity .
Example 2: General materials, methods and definitions of functional annotations
The methods section contains both information on statistical analyses used for identification of differentially expressed genes and detailed annotation data of identified microarray probesets. Affymetrix Probeset Annotation
All annotation data of GeneChip® arrays are extracted from the NetAffx™ Analysis Center (internet website: www.affymetrix.com). Files for U133 set arrays, including U133A and U133B microarrays are derived from the June 2003 release.
The original publication refers to: Liu G, Loraine AE, Shigeta R, Cline M, Cheng J, Valmeekam V, Sun S, Kulp D, Siani-Rose MA. NetAffx: Affymetrix probesets and annotations. Nucleic Acids Res. 2003;31(l):82-6.
The sequence data are omitted due to their large size, and because they do not change, whereas the annotation data are updated periodically, for example new information on chromomal location and functional annotation of the respective gene products. Sequence data are available for download in the NetAffx Download Center (www.affymetrix.com)
Data fields:
In the following section, the content of each field of the data files are described. Microarray probesets, for example found to be differentially expressed between different types of leukemia samples are further described by additional information. The fields are of the following types:
1. GeneChip Array Information
2. Probe Design Information
3. Public Domain and Genomic References
1. GeneChip Array Information
HG-U133 ProbeSet D:
HG-U133 ProbeSet_ID describes the probe set identifier. Examples are: 200007_at, 20001 l_s_at, 200012_x_at.
GeneChip:
The description of the GeneChip probe array name where the respective probeset is represented. Examples are: Affymetrix Human Genome U133A Array or Affymetrix Human Genome U133B Array.
2. Probe Design Information Sequence Type:
The Sequence Type indicates whether the sequence is an Exemplar, Consensus or Control sequence. An Exemplar is a single nucleotide sequence taken directly from a public database. This sequence could be an mRNA or EST. A Consensus sequence, is a nucleotide sequence assembled by Affymetrix, based on one or more sequence taken from a public database.
Transcript ID: The cluster identification number with a sub-cluster identifier appended.
Sequence Derived From:
The accession number of the single sequence, or representative sequence on which the probe set is based. Refer to the "Sequence Source" field to determine the database used.
Sequence ID:
For Exemplar sequences: Public accession number or GenBank identifier. For Consensus sequences: Affymetrix identification number or public accession number.
Sequence Source:
The database from which the sequence used to design this probe set was taken. Examples are: GenBank®, RefSeq, UniGene, TIGR (annotations from The Institute for Genomic Research).
3. Public Domain and Genomic References
Most of the data in this section come from LocusLink and UniGene databases, and are annotations of the reference sequence on which the probe set is modeled.
Gene Symbol and Title:
A gene symbol and a short title, when one is available. Such symbols are assigned by different organizations for different species. Affymetrix annotational data come from the UniGene record. There is no indication which species-specific databank was used, but some of the possibilities include for example HUGO: The Human Genome Organization. MapLocation:
The map location describes the chromosomal location when one is available.
Unigene_Accession:
UniGene accession number and cluster type. Cluster type can be "full length" or "est", or " — " if unknown.
LocusLink: This information represents the LocusLink accession number.
Full Length Ref. Sequences:
Indicates the references to multiple sequences in RefSeq. The field contains the ID and description for each entry, and there can be multiple entries per probeSet.
Example 3: Sample preparation, processing and data analysis
Method 1:
Microarray analyses were performed utilizing the GeneChip® System (Affymetrix, Santa Clara, USA). Hybridization target preparations were performed according to recommended protocols (Affymetrix Technical Manual). In detail, at time of diagnosis, mononuclear cells were purified by FicoU-Hypaque density centrifugation. They had been lysed immediately in RLT buffer (Qiagen, Hilden, Germany), frozen, and stored at -80°C from 1 week to 38 months. For gene expression profiling cell lysates of the leukemia samples were thawed, homogenized (QIAshredder, Qiagen), and total RNA was extracted (RNeasy Mini Kit, Qiagen). Subsequently, 5-10 μg total RNA isolated from 1 x 107 cells was used as starting material for cDNA synthesis with oligo [(dT)2 T7ρromotor]65 primer (cDNA Synthesis System, Roche Applied Science, Mannheim, Germany). cDNA products were purified by phenol/clilorophorm/IAA extraction (Ambion,
Austin, USA) and acetate/ethanol-precipitated overnight. For detection of the hybridized target nucleic acid biotin-labeled ribonucleotides were incorporated during the following in vitro transcription reaction (Enzo BioArray HighYield RNA Transcript Labeling Kit, Enzo Diagnostics). After quantification by spectrophotometric measurements and 260/280 absorbance values assessment for quality control of the purified cRNA (RNeasy Mini Kit, Qiagen), 15 μg cRNA was fragmented by alkaline treatment (200 mM Tris-acetate, pH 8.2/500 mM potassium acetate/150 mM magnesium acetate) and added to the hybridization cocktail sufficient for five hybridizations on standard GeneChip microarrays (300 μl final volume). Washing and staining of the probe arrays was performed according to the recommended Fluidics Station protocol (EukGE-WS2v4). Affymetrix Microarray Suite software (version 5.0.1) extracted fluorescence signal intensities from each feature on the microarrays as detected by confocal laser scanning according to the manufacturer's recommendations.
Expression analysis quality assessment parameters included visiual array inspection of the scanned image for the presence of image artifacts and correct grid alignment for the identification of distinct probe cells as well as both low 375' ratio of housekeeping controls (mean: 1.90 for GAPDH) and high percentage of detection calls (mean: 46.3% present called genes). The 3' to 5' ratio of GAPDH probesets can be used to assess RNA sample and assay quality. Signal values of the
3' probe sets for GAPDH are compared to the Signal values of the corresponding 5' probe set. The ratio of the 3' probe set to the 5' probe set is generally no more than 3.0. A high 3' to 5' ratio may indicate degraded RNA or inefficient synthesis of ds cDNA or biotinylated cRNA (GeneChip® Expression Analysis Technical Manual, www.affymetrix.com). Detection calls are used to determine whether the transcript of a gene is detected (present) or undetected (absent) and were calculated using default parameters of the Microarray Analysis Suite MAS 5.0 software package.
Method 2:
Bone marrow (BM) aspirates are taken at the time of the initial diagnostic biopsy and remaining material is immediately lysed in RLT buffer (Qiagen), frozen and stored at -80 C until preparation for gene expression analysis. For microarray analysis the GeneChip System (Affymetrix, Santa Clara, CA, USA) is used. The targets for GeneChip analysis are prepared according to the current Expression
Analysis. Briefly, frozen lysates of the leukemia samples are thawed, homogenized (QIAshredder, Qiagen) and total RNA extracted (RNeasy Mini Kit, Qiagen) .Normally 10 ug total RNA isolated from 1 x 107 cells is used as starting material in the subsequent cDNA-Synthesis using Oligo-dT-T7-Promotor Primer (cDNA synthesis Kit, Roche Molecular Biochemicals). The cDNA is purified by phenol-chlorophorm extraction and precipitated with 100% Ethanol over night. For detection of the hybridized target nucleic acid biotin-labeled ribonucleotides are incorporated during the in vitro transcription reaction (Enzo® BioArray™ HighYield™ RNA Transcript Labeling Kit, ENZO). After quantification of the purified cRNA (RNeasy Mini Kit, Qiagen), 15 ug are fragmented by alkaline treatment (200 mM Tris-acetate, pH 8.2, 500 mM potassium acetate, 150 mM magnesium acetate) and added to the hybridization cocktail sufficient for 5 hybridizations on standard GeneChip microarrays. Before expression profiling Test3 Probe Arrays (Affymetrix) are chosen for monitoring of the integrity of the cRNA. Only labeled cRNA-cocktails which showed a ratio of the messured intensity of the 3' to the 5' end of the GAPDH gene less than 3.0 are selected for subsequent hybridization on HG-U133 probe arrays (Affymetrix). Washing and staining the Probe arrays is performed as described (siehe Affymetrix-Original- Literatur (LOCKHART und LIPSHUTZ). The Affymetrix software (Microarray Suite, Version 4.0.1) extracted fluorescence intensities from each element on the arrays as detected by confocal laser scanning according to the manufacturers recommendations .
35 a e +
Table 1
1. One-Versus-AII (OVA)
1.1 11q23 versus rest
# affy id HUGO name fc p q stn t Map Location 1 205453_at HOXB2 -9.16 5.54E-34 1.71E-29 -0.92 -14.34 17q21- q22 2 225344_at ERAP140 -3.54 9.79E-33 1.51 E-28 -0.91 -14.04 6q22.33 3 226517_at BCAT1 -7.37 3.52E-29 3.64E-25 -0.83 -12.91 12pter- q12 4 200923_at LGALS3BP -7.42 7.40E-28 5.73E-24 -0.82 -12.60 17q25 5 202746_at ITM2A -7.88 1.46E-27 9.04E-24 -0.80 -12.43 Xq13.3- Xq21.2 6 236513_at -2.80 1.45E-25 5.00E-22 -0.80 -12.18 7 206761_at TACTILE -11.19 3.98E-26 2.05E-22 -0.78 -12.03 3q13.13 8 205624_at CPA3 -12.31 6.26E-26 2.77E-22 -0.78 -11.99 3q21-q25 9 202747_s_at ITM2A -7.67 1.83E-25 5.65E-22 -0.77 -11.86 Xq13.3- Xq21.2 10 213258_at -9.52 1.15E-25 4.44E-22 -0.77 -11.85 11 211137_s_at ATP2C1 -1.93 1.24E-23 2.96E-20 -0.79 -11.85 3q21-q24 12 228904_at -9.68 9.09E-25 2.56E-21 -0.77 -11.69 13 201830_s_at NET1 -3.02 5.42E-22 9.87E-19 -0.79 -11.56 10p15 14 210664_s_at TFPI -6.02 2.08E-24 5.37E-21 -0.74 -11.43 2q31- q32.1 15 220306_at FLJ20202 -3.65 3.19E-23 7.05E-20 -0.75 -11.41 1p11.1 16 221235_s_at -2.09 8.31 E-22 1.35E-18 -0.77 -11.41 17 225831_at LOC148894 -2.83 2.74E-20 3.39E-17 -0.78 -11.22 1p36.11 18 241756_at -2.87 3.92E-18 2.86E-15 -0.81 -11.04 19 214390_s_at BCAT1 -5.82 2.42E-22 4.99E-19 -0.72 -10.96 12pter- q12 20 210993_s_at MADH1 -5.11 7.86E-22 1.35E-18 -0.71 -10.86 4q28 21 205366_s_at HOXB6 -15.75 4.15E-22 8.03E-19 -0.70 -10.78 17q21.3 22 221760_at MAN1A1 -4.63 1.12E-21 1.73E-18 -0.69 -10.64 6q22 23 213549_at PRO2730 -2.72 1.95E-20 2.51 E-17 -0.70 -10.53 3p21.31 24 239791_at -12.97 3.55E-21 5.24E-18 -0.68 -10.48 25 201829_at NET1 -2.10 1.65E-18 1.34E-15 -0.73 -10.47 10p15 26 210665_at TFPI -8.51 5.06E-21 7.13E-18 -0.67 -10.40 2q31- q32.1 27 236892_s_at -11.68 9.17E-21 1.23E-17 -0.69 -10.40 28 225285_at -6.04 3.20E-19 3.19E-16 -0.70 -10.35 29 224049_at KCNK17 -2.52 1.71 E-19 1.82E-16 -0.69 -10.32 6p21.1 30 242051_at -3.10 4.34E-20 4.80E-17 -0.68 -10.32 31 222920_s_at KIAA0748 -4.32 2.34E-19 2.41 E-16 -0.68 -10.25 12q13.13 32 201242_s_at ATP1 B1 -3.87 3.62E-18 2.73E-15 -0.70 -10.20 1q22-q25 33 219686_at HSA250839 -6.75 3.92E-20 4.50E-17 -0.66 -10.12 4p16.2 34 219188_s_at LRP16 -2.90 3.01 E-18 2.33E-15 -0.69 -10.10 11q11 35 227297_at -7.34 3.84E-20 4.50E-17 -0.65 -10.08 36 233849_s_at ARHGAP5 -5.80 9.16E-19 8.10E-16 -0.67 -10.07 14q12 37 208116 s at MAN1A1 -3.24 5.28E-19 4.95E-16 -0.67 -10.06 6q22 36 a e +
38 236198_at -4.75 1.34E-18 1.12E-15 0.67 -10.01
39 225974_at DKFZp762C1112 -4.33 8.06E-17 5.09E-14 0.70 -9.97 8q21.3
40 218966_at MY05C -2.12 2.38E-16 1.37E-13 0.70 -9.86 15q21
41 226867_at FLJ20686 -2.39 6.88E-19 6.26E-16 0.65 -9.86 9p21.3
42 200829_x_at ZNF207 -1.46 2.97E-14 1.12E-11 0.78 -9.85 17q11.2
43 226342_at -4.49 4.30E-19 4.16E-16 0.64 -9.82
44 203544_s_at STAM -2.52 3.50E-16 1.97E-13 0.70 -9.79 10p14- p13
45 235142_at MGC17919 -3.58 1.25E-18 1.08E-15 0.63 -9.68 1p34.3
46 225830_at LOC118987 -2.42 6.92E-18 4.87E-15 0.63 -9.58 10q26.12
47 204951 _at ARHH -2.95 3.86E-15 1.73E-12 0.70 -9.54 4p13
48 241133_at TRB -5.63 1.93E-18 1.53E-15 0.62 -9.54 7q34
49 243888_at -2.64 8.83E-17 5.47E-14 0.65 -9.50
50 200953 s at CCND2 -2.64 5.88E-16 3.03E-13 0.66 -9.46 12p13
1.2 inv(16) versus rest
# affy id HUGO name fc p q stn t Map Location 1 202370_s_at CBFB -2.72 4.30E-36 2.40E-32 -1.24 -18.06 16q22.1 2 227567_at -4.70 1.45E-32 3.37E-29 -1.27 -17.96 3 225055_at DKFZp667M2411 -4.70 6.24E-34 1.74E-30 -1.25 -17.94 17q11.2 4 213737_x_at -2.52 6.40E-37 4.46E-33 -1.12 -16.75 5 214651_s_at HOXA9 -14.42 4.42E-42 1.23E-37 -1.08 -16.73 7p15-p14 6 232636_at DKFZp547M2010 -10.42 1.43E-39 1.99E-35 -1.04 -16.09 Xq27.3 7 235753_at -8.08 3.36E-39 3.12E-35 -1.04 -15.99 8 226352_at -5.30 2.49E-34 7.71 E-31 -1.00 -15.19 9 209905_at HOXA9 -42.52 5.18E-36 2.41 E-32 -0.99 -15.12 7p15-p14 10 225102_at LOC 152009 -4.70 2.64E-32 5.66E-29 -1.00 -14.99 3q21.3 11 211031_s_at CYLN2 -6.51 4.91 E-35 1.96E-31 -0.95 -14.67 7q11.23 12 228497_at FLIPT1 -4.94 2.40E-34 7.71 E-31 -0.93 -14.48 1p13.1 13 223471_at RAB3IP -3.17 4.25E-25 3.48E-22 -1.01 -14.25 14 219218_at FLJ23058 -5.83 2.86E-33 7.25E-30 -0.92 -14.21 17q25.3 15 224952_at DKFZP564D166 -3.66 6.61 E-20 2.30E-17 -1.11 -14.20 17q23.3 16 206847_s_at HOXA7 -4.55 2.66E-31 4.66E-28 -0.93 -14.15 7p15-p14 17 222786_at C4S-2 -3.19 1.39E-31 2.78E-28 -0.91 -13.96 7p22 18 218414_s_at NUDE1 -2.01 9.62E-25 7.25E-22 -0.97 -13.82 16p13.11 19 229215_at ASCL2 -6.48 8.02E-31 1.32E-27 -0.90 -13.72 11p15.5 20 227224_at FLJ25604 -4.55 3.91 E-25 3.30E-22 -0.96 -13.70 1q24.2 21 201669_s_at MARCKS -10.42 2.68E-31 4.66E-28 -0.87 -13.52 6q22.2 22 200675_at CD81 -3.13 1.13E-18 3.47E-16 -1.05 -13.35 11 p15.5 23 213150_at HOXA10 -6.78 1.59E-30 2.47E-27 -0.86 -13.32 7p15-p14 24 235521_at HOXA3 -13.38 2.92E-30 4.28E-27 -0.87 -13.30 7p15-p14 25 230894_s_at -8.98 6.25E-29 7.92E-26 -0.86 -13.14 26 213779_at LOC129080 -3.11 5.69E-27 6.35E-24 -0.88 -13.12 22q12.1 27 223044_at SLC11A3 -7.75 1.88E-28 2.28E-25 -0.86 -13.08 2q32 28 217963_s_at NGFRAP1 -10.36 3.75E-29 4.98E-26 -0.85 -13.06 Xq22.1 29 235391 at LOC137392 -7.67 1.57E-29 2.19E-26 -0.84 -12.99 8q21.3 37 a e +
30 209406_at BAG2 -3.60 1.47E-26 1.58E-23 -0.84 -12.70 6p12.3- p11.2
31 211026_s_at MGLL -2.54 3.79E-24 2.71 E-21 -0.84 -12.45 3q21.3
32 241706_at LOC144402 -5.02 1.29E-25 1.20E-22 -0.82 -12.36 12q11
33 200985_s_at CD59 -6.42 3.05E-26 3.15E-23 -0.81 -12.35 11p13
34 226817_at -5.26 3.78E-27 4.39E-24 -0.80 -12.31
35 241985_at FLJ37870 -5.40 3.83E-25 3.30E-22 -0.82 -12.31 5q13.3
36 201432_at CAT -2.02 1.25E-16 2.77E-14 -0.99 -12.30 11p13
37 213353_at ABCA5 -3.06 9.05E-18 2.32E-15 -0.94 -12.22 17q24.3
38 216920_s_at TRGV9 -4.25 3.65E-25 3.28E-22 -0.80 -12.12 7p15
39 200984_s_at CD59 -3.07 2.15E-23 1.25E-20 -0.81 -12.04 11p13
40 218477_at PTD011 -2.68 3.02E-21 1.34E-18 -0.84 -12.02 6p12.1
41 220668_s_at DNMT3B -2.83 5.32E-24 3.54E-21 -0.80 -11.99 20q11.2
42 219304_s_at SCDGF-B -2.99 8.28E-26 8.25E-23 -0.78 -11.97 11 q22.3
43 218795_at ACP6 -3.21 1.17E-18 3.56E-16 -0.88 -11.89 1q21
44 204197_s_at RUNX3 -2.89 8.95E-24 5.67E-21 -0.79 -11.88 1p36
45 213908_at -5.96 1.15E-25 1.11E-22 -0.76 -11.82
46 215806_x_at TRGC2 -3.94 1.04E-23 6.30E-21 -0.78 -11.77 7p15
47 213241_at -3.73 4.96E-25 3.95E-22 -0.76 -11.71
48 213147_at HOXA10 -3.83 6.75E-21 2.65E-18 -0.81 -11.69 7p15-p14
49 235749_at UGCGL2 -4.91 9.42E-24 5.84E-21 -0.77 -11.63 13q32.1
50 213002_at MARCKS -3.08 8.04E-25 6.23E-22 -0.75 -11.60 6q22.2
1.3 inv(3) versus rest
ϊ affy id HUGO name fc p q s stn t Map Location 1 205382_s_at DF -5.92 8.32E-28 1.98E-23 -1.12 -15.98 19p13.3 2 230480_at HIWI2 -3.35 1.38E-21 4.70E-18 -0.86 -12.44 11 q21 3 204647_at HOMER3 -4.67 4.41 E-22 2.09E-18 -0.79 -11.77 19p13.11 4 210115_at RPL39L -6.00 3.06E-25 3.63E-21 -0.75 -11.69 3q27 5 204301_at KIAA0711 -6.79 7.34E-25 5.81 E-21 -0.76 -11.68 8p23.2 6 223703_at CDA017 -2.62 1.91 E-15 1.97E-12 -0.86 -11.38 10q23.1 7 204082_at PBX3 -4.18 2.02E-20 5.34E-17 -0.76 -11.22 9q33-q34 8 213110_s_at COL4A5 -11.30 4.39E-23 2.61 E-19 -0.71 -11.03 Xq22 9 212318_at TRN-SR -2.17 1.20E-11 3.52E-09 -0.97 -11.02 7q32.2
10 231300_at LOC90835 -2.80 2.55E-13 1.35E-10 -0.88 -11.01 16p11.2
11 204548_at STAR -6.67 1.21 E-21 4.70E-18 -0.70 -10.78 8p11.2
12 212953_x_at CALR -2.13 1.05E-20 3.12E-17 -0.71 -10.75 19p13.3- p13.2
13 226789_at -2.38 1.36E-12 5.86E-10 -0.87 -10.66
14 214575_s_at AZU1 -5.42 8.17E-16 9.25E-13 -0.77 -10.61 19p13.3
15 202759_s_at AKAP2 -2.93 7.67E-14 5.21 E-11 -0.81 -10.54 9q31-q33
16 204921_at GAS8 -2.67 2.30E-19 4.55E-16 -0.71 -10.52 16q24.3
17 200700_s_at KDELR2 -2.21 1.60E-12 6.66E-10 -0.84 -10.39 7p22.2
18 201186_at LRPAP1 -2.60 6.43E-15 5.87E-12 -0.76 -10.39 4p16.3
19 205767_at EREG -7.12 4.02E-20 8.69E-17 -0.68 -10.35 4q21.1
20 205624_at CPA3 -6.98 2.71 E-20 6.45E-17 -0.67 -10.27 3q21-q25 38 a e +
21 242621_at FLJ32468 -1.46 3.56E-12 1.25E-09 -0.82 -10.15 7q22.1
22 203746_s_at HCCS -1.50 6.88E-17 9.62E-14 -0.70 -10.11 Xp22.3
23 208967_s_at AK2 -2.29 8.09E-15 6.63E-12 -0.70 -9.76 1p34
24 205131_x_at SCGF -4.79 2.56E-16 3.21 E-13 -0.66 -9.69 19q13.3
25 236892_s_at -7.73 8.30E-19 1.52E-15 -0.62 -9.66
26 213893_x_at PMS2L5 -1.89 1.14E-09 1.70E-07 -0.90 -9.64 7q11-q22
27 213844_at H0XA5 -5.15 5.19E-15 5.14E-12 -0.68 -9.58 7p15-p14
28 226123_at LOC286180 -3.22 2.00E-12 8.04E-10 -0.74 -9.58 8q12.1
29 218865_at FLJ22390 -6.90 3.52E-18 5.98E-15 -0.61 -9.46 1q42.11
30 232250_at KIAA1257 -3.08 6.20E-13 2.95E-10 -0.69 -9.34 3q21.3
31 235077_at -3.90 2.97E-17 4.42E-14 -0.61 -9.28
32 239791_at -6.95 1.33E-17 2.11E-14 -0.60 -9.27
33 217499_x_at -1.53 9.73E-12 3.04E-09 -0.72 -9.23
34 231736_x_at MGST1 -3.33 1.39E-09 1.99E-07 -0.84 -9.22 12p12.3- p12.1
35 228161_at RAB32 -1.74 1.42E-13 8.46E-11 -0.66 -9.18 6q24.2
36 210783_x_at SCGF -4.49 1.60E-14 1.23E-11 -0.64 -9.18 19q13.3
37 239656_at -2.09 3.79E-12 1.31 E-09 -0.70 -9.17
38 227929_at -6.47 1.67E-16 2.20E-13 -0.60 -9.15
39 210006_at DKFZP5640243 -1.70 4.60E-11 1.07E-08 -0.73 -9.14 3p21.1
40 223534_s_at RPS6KL1 -1.78 5.76E-10 9.50E-08 -0.79 -9.12 14q24.2
41 203675_at NUCB2 -2.23 6.37E-10 1.04E-07 -0.79 -9.08 11p15.1- p14
42 228293_at LOC91614 -4.40 3.58E-11 8.69E-09 -0.72 -9.04 11p13
43 243917_at -1.39 1.17E-12 5.25E-10 -0.66 -8.95
44 211048_s_at ERP70 -2.09 6.36E-12 2.16E-09 -0.67 -8.93 7q35
45 226556_at -2.59 6.68E-10 1.08E-07 -0.76 -8.90
46 203421_at PIG11 -3.06 7.66E-16 9.10E-13 -0.58 -8.88 11p11.2
47 231415_at WBSCR22 -2.61 7.66E-15 6.63E-12 -0.60 -8.85
48 240672_at -1.45 2.71 E-12 1.00E-09 -0.65 -8.82
49 219588_s_at FLJ20311 -2.22 1.23E-10 2.47E-08 -0.71 -8.80 7q36.3
50 204332 s at AGA -1.66 1.23E-11 3.57E-09 -0.66 -8.78 4q32-q33
1.4 normal versus rest
t affy id HUGO name fc p q stn t Map Location 1 205600_x_at HOXB5 2.30 6.96E-29 1.51 E-24 0.95 13.64 17q21.3 2 205601_s_at HOXB5 3.09 6.49E-27 7.07E-23 0.94 13.15 17q21.3 3 228904_at 8.93 8.57E-26 5.91 E-22 1.04 13.10 4 236892_s_at 17.81 3.14E-24 9.76E-21 1.05 12.54 5 205366_s_at HOXB6 15.23 1.24E-24 5.41 E-21 0.94 12.52 17q21.3 6 239791 _at 15.87 3.58E-24 9.76E-21 1.02 12.50 7 205453_at HOXB2 3.87 1.09E-25 5.91 E-22 0.79 12.06 17q21- q22 8 231767_at HOXB4 2.86 2.89E-24 9.76E-21 0.82 11.92 17q21- q22 9 230743_at 2.18 2.42E-21 5.27E-18 0.79 11.06
10 229194 at 1.97 3.15E-22 7.62E-19 0.70 10.78 39 a e +
11 219304_s_at SCDGF-B 2.56 2.92E-20 5.77E-17 0.71 10.45 11 q22.3
12 216973_s_at H0XB7 3.97 7.64E-18 1.39E-14 0.75 9.91 17q21.3
13 213110_s_at COL4A5 5.14 2.76E-17 4.29E-14 0.67 9.52 Xq22
14 204779_s_at H0XB7 4.49 8.50E-17 1.16E-13 0.71 9.48 17q21.3
15 238058_at 2.13 2.42E-17 4.06E-14 0.62 9.34
16 232424_at PRDM16 10.27 2.89E-16 3.50E-13 0.74 9.32 1p36.23- p33
17 235749_at UGCGL2 2.82 7.12E-17 1.03E-13 0.60 9.13 13q32.1
18 240151_at 1.88 9.18E-17 1.18E-13 0.59 9.04
19 201427_s_at SEPP1 4.63 9.91 E-16 1.14E-12 0.60 8.84 5q31
20 225362_at LOG 159090 1.36 1.45E-15 1.57E-12 0.55 8.55 Xq26.3
21 232979_at 2.78 1.08E-14 9.43E-12 0.60 8.51
22 AFFX- ACTB -1.58 2.93E-15 3.04E-12 ■0.55 -8.49 7p15-p12 HSAC07/X00351_M_at - HG-U133B
23 225971 _at 1.64 4.26E-15 4.22E-12 0.54 8.40
24 209406_at BAG2 2.17 5.62E-15 5.32E-12 0.54 8.36 6p12.3- p11.2
25 209112 at CDKN1B 1.58 9.51 E-15 8.63E-12 0.53 8.27 12p13.1- p12
26 AFFX- ACTB -1.81 3.02E-14 2.35E-11 -0.54 -8.19 7p15-p12 HSAC07/X00351_5_at ■ HG-U133A
27 207111_at EMR1 2.82 5.08E-14 3.59E-11 0.56 8.19 19p13.3
28 209679_s_at LOC57228 -2.09 5.11 E-14 3.59E-11 -0.55 -8.18 12q13.12
29 217848_s_at PP 1.58 2.02E-14 1.69E-11 0.53 8.16 10q11.1- q24
30 233467_s_at PHEMX 1.47 2.53E-14 2.04E-11 0.53 8.14 11p15.5
31 203591_s_at CSF3R -2.02 2.29E-13 1.26E-10 -0.58 -8.10 1p35- p34.3
32 200740_s_at SMT3H1 1.30 3.78E-14 2.84E-11 0.52 8.07 21q22.3
33 238498_at 2.45 5.81 E-14 3.96E-11 0.53 8.06
34 AFFX- ACTB -1.80 8.12E-14 5.36E-11 -0.53 -8.03 7p15-p12 HSAC07/X00351_5_at - HG-U133B
35 204778_x_at HOXB7 3.06 1.66E-13 1.01 E-10 0.55 8.0017q21.3
36 240180_at 1.78 1.13E-13 7.05E-11 0.53 7.98
37 AFFX- ACTB -1.53 8.49E-14 5.44E-11 -0.51 -7.957p15-p12 HSAC07/X00351_M_at - HG-U133A
38 243010_at MSI2 2.133.15E-13 1.61E-10 0.54 7.9017q23.1
39 200696_s_at GSN -1.754.44E-132.06E-10 -0.54 -7.889q33
40 224773_at NAV1 -2.86 1.42E-125.52E-10 -0.59 -7.86
41 204785_x_at 1FNAR2 1.56 1.79E-13 1.05E-10 0.51 7.8521q22.11
42 241464_s_at 1.93 1.95E-13 1.12E-10 0.51 7.84
43 240131_at 1.892.31 E-13 1.26E-10 0.50 7.79
44 228571_at 1.592.90E-13 1.54E-10 0.50 7.75
45 235587_at LOC202781 1.634.63E-132.10E-10 0.51 7.747q36.3
46 218258_at RPAC2 1.323.26E-13 1.61E-10 0.50 7.7313q12.13
47 213353_at ABCA5 1.693.20E-13 1.61 E-10 0.50 7.7217q24.3
48 238778_at FLJ32798 3.054.72E-132.10E-10 0.51 7.7210p11.1
49 235331_x_at 1.693.33E-13 1.61 E-10 0.50 7.72
50 201664 at SMC4L1 1.663.95E-13 1.87E-10 0.50 7.713q26.1 40 Table1+
1.5 t(15;17) versus rest
# t affy id HUGO name fc p q stn t Map Location 1 211990_at HLA-DPA1 -9.63 6.57E-58 4.20E-54 -1.57 -23.80 6p21.3 2 204425_at ARHGAP4 -16.60 6.18E-64 1.19E-59 -1.51 -23.49 Xq28 3 209732_at CLECSF2 -25.48 7.22E-60 6.93E-56 -1.46 -22.47 12p13- p12 4 213587_s_at LOC155066 -5.51 5.76E-55 2.76E-51 -1.35 -20.92 7q36.1 5 205771 _s_at AKAP7 -10.27 1.00E-53 3.86E-50 -1.36 -20.88 6q23 6 213147_at HOXA10 -14.75 3.38E-51 1.08E-47 -1.26 -19.48 7p15-p14 7 201923_at PRDX4 -5.89 7.32E-35 4.53E-32 -1.35 -19.35 Xp22.13 8 217848_s_at PP -4.03 5.52E-28 1.31 E-25 -1.41 -18.97 10q11.1- q24 9 214651_s_at HOXA9 - 3.00E-47 8.23E-44 -1.25 -18.66 7p15-p14 136.34 10 204362_at SCAP2 -12.68 5.38E-47 1.29E-43 -1.21 -18.60 7p21-p15 11 241742_at PRAM-1 -6.74 6.92E-45 1.21E-41 -1.18 -18.17 19p13.2 12 201719_s_at EPB41 L2 -10.75 1.09E-45 2.32E-42 -1.15 -17.87 6q23 13 201137_s_at HLA-DPB1 -9.36 1.40E-45 2.70E-42 -1.15 -17.84 6p21.3 14 204563_at SELL -6.03 7.71 E-39 8.70E-36 -1.19 -17.83 1q23-q25 15 225639_at SCAP2 -10.70 2.18E-39 2.62E-36 -1.19 -17.78 7p21-p15 16 200931_s_at VCL -3.68 3.04E-28 7.48E-26 -1.25 -17.32 10q22.1- q23 17 228113_at STAT3 -4.16 3.36E-27 6.90E-25 -1.26 -17.30 17q21 18 203948_s_at MPO 3.42 7.87E-17 3.92E-15 1.62 17.17 17q23.1 19 216899_s_at SCAP2 -6.04 2.37E-38 2.29E-35 -1.10 -16.64 7p21-p15 20 227598_at LOC113763 -4.11 2.06E-33 1.04E-30 -1.12 -16.53 7q35 21 217478_s_at HLA-DMA -5.05 1.58E-32 7.14E-30 -1.12 -16.45 6p21.3 22 235753_at -9.53 1.82E-40 2.91 E-37 -1.07 -16.39 23 214797_s_at PCTK3 -4.71 2.20E-25 3.49E-23 -1.20 -16.36 1q31-q32 24 232617_at CTSS -5.24 2.36E-40 3.49E-37 -1.06 -16.34 1q21 25 213l50_at HOXA10 -26.84 4.98E-40 6.37E-37 -1.06 -16.28 7p15-p14 26 212953_x_at CALR 3.48 4.59E-13 1.32E-11 2.30 16.20 19p13.3- p13.2 27 236322_at -6.02 1.85E-29 5.00E-27 -1.13 -16.19 28 211991_s_at HLA-DPA1 -14.16 2.90E-40 3.98E-37 -1.04 -16.18 6p21.3 29 236554_x_at EVER2 -3.49 4.34E-23 5.41 E-21 -1.22 -16.09 17q25.3 30 204361_s_at SCAP2 -8.90 1.49E-34 8.51 E-32 -1.07 -16.04 7p21-p15 31 221004_s_at ITM2C 5.98 3.40E-13 9.98E-12 2.13 16.03 2q37 32 209448_at HTAT1P2 -6.94 2.39E-38 2.29E-35 -1.03 -15.85 11p15.1 33 229041_s_at -23.25 2.21 E-38 2.29E-35 -1.03 -15.78 34 214450_at CTSW 7.22 1.11 E-12 2.97E-11 2.39 15.77 11q13.1 35 227353_at EVER2 -3.52 4.10E-20 3.55E-18 -1.26 -15.77 17q25.3 36 225386_s_at LOC92906 -19.67 3.32E-38 3.03E-35 -1.01 -15.62 2p22.2 37 210145_at PLA2G4A -6.27 6.85E-37 5.47E-34 -1.02 -15.60 1q25 38 211474_s_at SERP1NB6 -3.83 3.38E-30 1.01E-27 -1.07 -15.55 6p25 39 205453_at HOXB2 -12.69 6.60E-38 5.76E-35 -1.01 -15.54 17q21- q22 41 a e +
40 201753_s_at ADD3 -5.38 1.92E-30 6.23E-28 -1.06 -15.53 10q24.2- q24.3
41 238949_at FLJ31951 -7.08 3.38E-32 1.44E-29 -1.04 -15.51 5q33.3
42 209905_at HOXA9 - 4.48E-37 3.74E-34 -1.04 -15.49 7p15-p14 361.44
43 208306_x_at HLA-DRB4 -6.23 2.87E-28 7.16E-26 -1.07 -15.43 6p21.3
44 230264_s_at AP1S2 -5.32 5.62E-36 4.15E-33 -1.00 -15.38 Xp22.31
45 206847_s_at HOXA7 -5.99 1.90E-34 1.04E-31 -1.01 -15.36 7p15-p14
46 209312_x_at HLA-DRB1 -5.91 9.96E-27 1.80E-24 -1.08 -15.32 6p21.3
47 200654_at P4HB 2.22 2.38E-14 8.36E-13 1.58 15.26 17q25
48 38487_at STAB1 8.02 2.26E-12 5.70E-11 2.35 15.23 3p21.31
49 203949_at MPO 2.36 5.16E-19 3.78E-17 1.23 15.21 17q23.1 50 203299_s_at AP1S2 -4.02 2.19E-31 8.24E-29 -1.02 -15.14 Xp22.31
1.6 t(8;21) versus rest
# affy id HUGO name fc p q stn t Map Location 1 214651_s_at HOXA9 - 4.83E-47 1.40E-42 -1.24 -18.57 7p15-p14 119.43 2 221581_s_at WBSCR5 -5.89 1.92E-42 1.86E-38 -1.17 -17.78 7q11.23 3 213147_at HOXA10 -9.51 2.99E-43 4.35E-39 -1.14 -17.48 7p15-p14 4 225615_at LOC126917 -6.42 9.85E-38 3.58E-34 -1.12 -16.85 1p36.13 5 213150_at HOXA10 -32.72 2.09E-40 1.52E-36 -1.07 -16.40 7p15-p14 6 235753_at -8.55 2.77E-39 1.61 E-35 -1.03 -15.94 7 215087_at -3.53 5.35E-37 1.63E-33 -1.04 -15.84 8 205453_at HOXB2 -14.60 1.66E-38 8.05E-35 -1.02 -15.71 17q21- q22 9 206847_s_at HOXA7 -5.31 6.33E-38 2.63E-34 -1.02 -15.71 7p15-p14 10 209905_at HOXA9 - 5.62E-37 1.63E-33 -1.03 -15.44 7p15-p14 314.99 11 226865_at -5.92 1.20E-35 3.17E-32 -0.95 -14.82 12 224764_at ARHGAP10 -5.16 4.47E-31 7.65E-28 -0.99 -14.79 10 13 204494_s_at DKFZP434H132 -2.99 1.64E-29 2.52E-26 -0.98 -14.58 15q22.33 14 238077_at MGC27385 -3.63 6.81 E-28 7.92E-25 -0.99 -14.51 3p21.1 15 204069_at MEIS1 -11.83 1.42E-33 3.19E-30 -0.93 -14.29 2p14-p13 16 217963_s_at NGFRAP1 -14.47 1.40E-33 3.19E-30 -0.92 -14.20 Xq22.1 17 204495_s_at DKFZP434H132 -2.85 3.29E-29 4.55E-26 -0.94 -14.09 15q22.33 18 227279_at MGC15737 -2.56 1.66E-18 5.95E-16 -1.09 -13.93 Xq22.1 19 201425_at ALDH2 -6.63 2.09E-31 4.05E-28 -0.90 -13.86 12q24.2 20 241370_at -3.00 8.73E-27 9.76E-24 -0.94 -13.79 21 213844_at HOXA5 -11.73 1.36E-31 2.82E-28 -0.88 -13.60 7p15-p14 22 235521_at HOXA3 -16.52 4.29E-31 7.65E-28 -0.89 -13.59 7p15-p14 23 206310_at SPINK2 -44.78 9.85E-31 1.59E-27 -0.89 -13.50 4q12 24 208890_s_at PLXNB2 -3.59 3.80E-22 2.30E-19 -0.95 -13.35 22q13.33 25 208091_s_at DKFZP564K0822 -5.01 1.98E-24 1.64E-21 -0.91 -13.26 7p14.1 26 203017_s_at SSX2IP -3.40 2.78E-22 1.76E-19 -0.93 -13.11 27 209500_x_at TNFSF13 -3.21 6.68E-24 5.25E-21 -0.90 -13.05 17p13.1 28 238455_at -3.93 1.88E-28 2.28E-25 -0.85 -13.04 29 228365_at LOC 144402 -6.68 2.03E-29 2.95E-26 -0.83 -12.95 12q11 42 a e
30 206120_at CD33 -4.08 1.19E-25 1.15E-22 -0.86 -12.81 19q13.3
31 227995_at -7.24 1.13E-28 1.50E-25 -0.83 -12.79
32 233955_x_at HSPC195 -2.89 1.70E-24 1.45E-21 -0.86 -12.75 5q31.3
33 208146_s_at CPVL -12.53 1.82E-28 2.28E-25 -0.82 -12.67 7p15-p14
34 243806_at -3.96 1.45E-25 1.36E-22 -0.84 -12.63
35 203680_at PRKAR2B -5.25 4.03E-26 4.34E-23 -0.83 -12.57 7q22- q31.1
36 210314_x_at TNFSF13 -3.71 1.67E-20 7.82E-18 -0.87 -12.25 17p13.1
37 236297_at -3.21 9.86E-26 9.89E-23 -0.80 -12.16
38 224516_s_at HSPC195 -2.91 1.46E-24 1.29E-21 -0.78 -11.91 5q31.3
39 240572_s_at -3.33 2.37E-19 9.42E-17 -0.85 -11.90
40 213908_at -5.85 8.32E-26 8.63E-23 -0.77 -11.87
41 227276_at TEM7R -2.80 1.50E-20 7.13E-18 -0.83 -11.85 10p12.1
42 224049_at KCNK17 -2.57 1.14E-24 1.03E-21 -0.77 -11.75 6p21.1
43 222996_s_at HSPC195 -2.31 5.41 E-23 3.83E-20 -0.79 -11.75 5q31.3
44 227853_at -2.88 4.65E-15 7.56E-13 -0.94 -11.73
45 220974_x_at BA108L7.2 -4.10 7.98E-18 2.42E-15 -0.86 -11.69 10q24.31
46 225245_x_at H2AFJ -3.55 2.11 E-19 8.66E-17 -0.83 -11.66 12p12
47 217226_s_at BA108L7.2 -2.93 4.27E-17 1.05E-14 -0.87 -11.65 10q24.31
48 201951_at ALCAM -3.93 8.41 E-20 3.60E-17 -0.81 -11.60 3q13.1
49 230894_s_at -5.85 1.11 E-22 7.53E-20 -0.77 -11.60
50 223398_at MGC11115 -2.54 1.74E-16 3.95E-14 -0.88 -11,57 9q22.2
Table 2
2. All-Pairs (AP)
2.1 11q23 versus inv(16)
# affy id HUGO name fc p q stn t Map Location 1 213737_x_at 3.73 1.13E-15 1.73E-11 2.10 13.96 2 200665_s_at SPARC -16.71 3.03E-13 1.32E-09 -2.29 -13.74 5q31.3- q32 3 200953_s_at CCND2 -4.22 1.13E-15 1.73E-11 -1.89 -13.24 12p13 4 214651_s_at HOXA9 24.48 6.34E-14 4.83E-10 2.09 12.83 7p15-p14 5 202746_at ITM2A -15.51 1.87E-12 5.21 E-09 -2.15 -12.76 Xq13.3- Xq21.2 6 202747_s_at ITM2A -15.29 3.80E-12 7.25E-09 -2.03 -12.22 Xq13.3- Xq21.2 7 231310_at -4.48 1.13E-14 1.15E-10 -1.64 -11.74 8 200951_s_at CCND2 -5.06 4.26E-13 1.63E-09 -1.72 -11.64 12p13 9 202551_s_at CRIM1 -4.41 2.93E-13 1.32E-09 -1.63 -11.30 2p21 10 206847_s_at HOXA7 6.89 1.31 E-12 4.43E-09 1.67 10.96 7p15-p14 11 227567_at 5.37 2.91 E-13 1.32E-09 1.58 10.93 12 201497_x_at MYH11 -25.07 1.61 E-10 1.34E-07 -2.11 -10.83 16p13.13- p13.12 13 205453_at HOXB2 -7.71 7.13E-12 1.28E-08 -1.64 -10.82 17q21- q22 14 235753_at 13.56 9.87E-12 1.51 E-08 1.80 10.62 15 201496_x_at MYH11 -6.90 6.26E-11 7.35E-08 -1.73 -10.60 16p13.13- 43 a e + p13.12 16 212667_at SPARC -8.20 5.65E-11 6.89E-08 -1.65 -10.40 5q31.3- q32 17 224049_at KCNK17 -4.41 9.00E-11 9.46E-08 -1.66 -10.31 6p21.1 18 213147_at HOXA10 6.19 3.53E-12 7.19E-09 1.50 10.20 7p15-p14 19 229215_at ASCL2 10.61 2.45E-11 3.40E-08 1.55 9.93 11p15.5 20 203949_at MPO -3.22 2.23E-12 5.29E-09 -1.38 -9.79 17q23.1 21 209905_at HOXA9 81.21 7.73E-11 8.74E-08 1.69 9.76 7p15-p14 22 226517_at BCAT1 -10.39 6.14E-10 3.82E-07 -1.62 -9.66 12pter- q12 23 202931_x_at BIN1 -2.97 2.31E-12 5.29E-09 -1.32 -9.58 2q14 24 213908_at 15.53 1.14E-10 1.10E-07 1.59 9.54 25 201830_s_at NET1 -4.02 1.63E-10 1.34E-07 -1.45 -9.52 10p15 26 223471_at RAB3IP 3.55 8.58E-12 1.45E-08 1.35 9.50 27 201029_s_at CD99 -1.93 2.43E-12 5.29E-09 -1.31 -9.48 Xp22.32 28 224952_at DKFZP564D166 3.54 1.88E-12 5.21 E-09 1.27 9.31 17q23.3 29 204082_at PBX3 5.48 1.81 E-10 1.45E-07 1.49 9.25 9q33-q34 30 228058_at LOG 124220 -5.44 9.13E-12 1.47E-08 -1.27 -9.16 16p13.3 31 225831_at LOC148894 -3.50 2.57E-10 1.96E-07 -1.35 -9.05 1p36.11 32 205330_at MN1 -16.11 4.51 E-09 1.52E-06 -1.71 -9.04 22q12.1 33 202370_s_at CBFB 3.04 1.34E-10 1.20E-07 1.36 9.03 16q22.1 34 225102_at LOC152009 5.50 1.44E-10 1.26E-07 1.34 8.98 3q21.3 35 210139_s_at PMP22 -8.84 3.42E-09 1.26E-06 -1.52 -8.92 17p12- p11.2 36 211012_s_at PML -2.72 4.71 E-11 5.99E-08 -1.22 -8.76 15q22 37 200602_at APP -6.17 1.23E-10 1.14E-07 -1.24 -8.73 21q21.3 38 203733_at MYLE 3.27 8.06E-11 8.78E-08 1.24 8.72 16p13.2 39 228496_s_at CRIM1 -2.82 1.15E-10 1.10E-07 -1.23 -8.70 2p21 40 226137_at -3.57 2.49E-09 1.07E-06 -1.38 -8.69 41 214452_at BCAT1 -4.11 1.17E-09 6.73E-07 -1.30 -8.60 12pter- q12 42 203329_at PTPRM -5.80 7.33E-09 2.17E-06 -1.48 -8.60 18p11.2 43 241706_at LOG 144402 6.03 4.36E-10 2.96E-07 1.26 8.52 12q11 44 213150_at HOXA10 11.20 1.28E-09 7.06E-07 1.38 8.51 7p15-p14 45 201828_x_at CXX1 2.80 1.75E-11 2.54E-08 1.15 8.51 Xq26 46 202265_at BMI1 3.17 4.25E-10 2.95E-07 1.25 8.48 10p11.23 47 210006_at DKFZP5640243 2.23 5.26E-10 3.42E-07 1.26 8.46 3p21.1 48 225285_at -9.01 3.35E-09 1.26E-06 -1.31 -8.44 49 242738_s_at -2.35 5.69E-10 3.62E-07 -1.22 -8.43 50 218966_at MY05C -2.93 2.74E-09 1.13E-06 -1.28 -8.36 15q21
2.2 11q23 versus inv(3) affy id HUGO name fc p q stn t Map Location 1 204082_at PBX3 8.05 2.96E-11 4.56E-07 1.56 9.79 9q33-q34 2 226789_at 3.17 7.24E-11 4.56E-07 1.31 8.77 3 225344_at ERAP140 -4.35 2.49E-07 4.83E-05 -1.77 -8.74 6q22.33 4 214651_s_at HOXA9 4.34 4.49E-11 4.56E-07 1.28 8.67 7p15-p14 44 Table1+2 5 222982_x_at SLC38A2 -1.93 7.96E-10 1.84E-06 -1.31 -8.55 12q 6 213893_x_at PMS2L5 2.34 7.87E-11 4.56E-07 1.26 8.53 7q11-q22 7 236398_s_at 6.39 2.46E-10 1.12E-06 1.29 8.52 8 235753_at 4.79 2.97E-10 1.12E-06 1.27 8.39 9 233955_x_at HSPC195 -4.27 9.34E-09 6.01 E-06 -1.34 -8.38 5q31.3
10 210006_at DKFZP5640243 2.30 3.38E-10 1.12E-06 1.26 8.35 3p21.1
11 235199_at -3.81 2.13E-07 4.41 E-05 -1.54 -8.32
12 203733_at MYLE 2.89 5.18E-10 1.33E-06 1.22 8.12 16p13.2
13 212318_at TRN-SR 2.59 4.46E-10 1.29E-06 1.21 8.10 7q32.2
14 202053_s_at ALDH3A2 2.81 1.73E-09 2.56E-06 1.22 7.94 17p11.2
15 214643_x_at BIN1 -4.34 2.80E-07 5.15E-05 -1.43 -7.94 2q14
16 209905_at HOXA9 6.89 1.61 E-09 2.56E-06 1.21 7.93 7p15-p14
17 228083_at CACNA2D4 8.25 1.77E-09 2.56E-06 1.21 7.91 12p13.33
18 225386_s_at LOC92906 6.11 1.05E-09 2.22E-06 1.17 7.84 2p22.2
19 223703_at CDA017 3.76 3.59E-09 3.24E-06 1.21 7.80 10q23.1
20 200602_at APP -9.73 7.82E-07 1.01 E-04 -1.48 -7.75 21q21.3
21 212782_x_at POLR2J 2.42 3.77E-09 3.24E-06 1.15 7.66 7q11.2
22 208116_s_at MA 1A1 -4.72 9.63E-07 1.16E-04 -1.47 -7.63 6q22
23 208967_s_at AK2 3.86 8.89E-09 5.89E-06 1.21 7.62 1p34
24 215667_x_at PMS2L5 1.93 2.43E-09 3.01 E-06 1.13 7.62 7q11-q22
25 225389_at BTBD6 2.27 1.62E-09 2.56E-06 1.12 7.60 14q32
26 221036_s_at PSFL 2.03 1.74E-09 2.56E-06 1.12 7.57 15q21.3
27 214430_at GLA 2.10 2.07E-09 2.82E-06 1.11 7.51 Xq22
28 206440_at LIN7A 8.97 8.85E-09 5.89E-06 1.16 7.49 12q21
29 230051 _at -4.16 5.08E-07 7.64E-05 -1.32 -7.48
30 209836_x_at MGC5178 2.05 2.47E-09 3.01 E-06 1.10 7.47 16p12.1
31 202961_s_at ATP5J2 2.24 5.44E-09 4.35E-06 1.11 7.45 7q22.1
32 212174_at AK2 3.70 6.56E-09 4.90E-06 1.13 7.45 1p34
33 213370_s_at SFMBT 1.98 3.04E-09 3.24E-06 1.10 7.44 3p21.31
34 222996_s_at HSPC195 -4.05 7.45E-07 9.81 E-05 -1.34 -7.43 5q31.3
35 202054_s_at ALDH3A2 4.23 2.86E-09 3.24E-06 1.09 7.42 17p11.2
36 224516_s_at HSPC195 -5.00 2.99E-07 5.38E-05 -1.26 -7.41 5q31.3
37 206847_s_at H0XA7 2.83 3.35E-09 3.24E-06 1.10 7.41 7p15-p14
38 201186_at LRPAP1 3.21 7.87E-09 5.70E-06 1.12 7.39 4p16.3
39 219126_at XAP135 1.82 3.30E-09 3.24E-06 1.09 7.38 6q27
40 219991_at SLC2A9 2.18 5.75E-09 4.44E-06 1.11 7.38 4p16- p15.3
41 202605_at GUSB 3.16 4.47E-09 3.70E-06 1.10 7.37 7q21.11
42 213908_at 3.92 1.51 E-08 8.34E-06 1.15 7.37
43 223207_x_at PHP14 1.80 3.42E-09 3.24E-06 1.09 7.36 9q34.3
44 220924_s_at SLC38A2 -1.62 3.76E-09 3.24E-06 -1.08 -7.34 12q
45 200654_at P4HB 2.25 8.68E-09 5.89E-06 1.09 7.28 17q25
46 206478_at KIAA0125 -13.74 3.61 E-06 2.61 E-04 -1.64 -7.27 14q32.33
47 218041_x_at SLC38A2 -1.65 1.58E-08 8.49E-06 -1.09 -7.21 12q
48 214453_s_at IFI44 -4.71 1.66E-06 1.59E-04 -1.34 -7.18 1p31.1
49 231300_at LOC90835 3.98 2.03E-08 9.99E-06 1.11 7.18 16p11.2
50 209696_at FBP1 4.25 3.05E-08 1.29E-05 1.14 7.17 9q22.3 45 a e +
2.3 11 q23 versus normal
# affy id HUGO name fc p q stn t Map Location 1 205453_at HOXB2 -12.20 1.96E-35 5.87E-31 -1.29 -16.31 17q21- q22 2 228904_at -14.32 2.38E-27 3.57E-23 -1.15 -13.75 3 205366_s_at HOXB6 -23.99 1.76E-25 1.76E-21 -1.06 -12.92 17q21.3 4 239791_at -19.84 1.54E-24 1.16E-20 -1.03 -12.55 5 236892_s_at -17.98 3.08E-24 1.85E-20 -1.05 -12.52 6 205601_s_at HOXB5 -3.14 1.36E-22 6.80E-19 -0.92 -11.60 17q21.3 7 231767_at HOXB4 -3.47 1.23E-21 5.25E-18 -0.91 -11.40 17q21- q22 8 211137_s_at ATP2C1 -1.99 9.13E-21 3.43E-17 -0.85 -10.86 3q21-q24 9 200923_at LGALS3BP -8.71 4.82E-20 1.45E-16 -0.89 -10.81 17q25 10 225344_at ERAP140 -3.36 1.70E-20 5.67E-17 -0.84 -10.72 6q22.33 11 213258_at -9.54 6.33E-20 1.73E-16 -0.85 -10.64 12 220306_at FLJ20202 -3.46 1.84E-19 4.61 E-16 -0.82 -10.41 1p11.1 13 210664_s_at TFPI -6.33 4.23E-19 9.07E-16 -0.82 -10.30 2q31- q32.1 14 236513_at -2.70 3.53E-19 8.15E-16 -0.80 -10.23 15 205600_x_at HOXB5 -1.84 1.63E-18 3.26E-15 -0.79 -10.03 17q21.3 16 222920_s_at KIAA0748 -4.54 2.86E-18 5.36E-15 -0.79 -9.96 12q13.13 17 210993_s_at MADH1 -5.23 9.34E-18 1.65E-14 -0.76 -9.69 4q28 18 232424_at PRDM16 -14.39 5.25E-17 8.29E-14 -0.80 -9.63 1p36.23- p33 19 205624_at CPA3 -10.95 7.38E-17 1.11 E-13 -0.77 -9.52 3q21-q25 20 226517_at BCAT1 -6.15 3.45E-17 5.75E-14 -0.74 -9.49 12pter- q12 21 200829_x_at ZNF207 -1.49 8.06E-15 6.36E-12 -0.80 -9.45 17q11.2 22 225974_at DKFZp762C1112 -4.61 2.88E-16 3.75E-13 -0.75 -9.39 8q21.3 23 216973_s_at HOXB7 -3.64 1.06E-16 1.51 E-13 -0.74 -9.37 17q21.3 24 241756_at -2.73 1.95E-15 2.02E-12 -0.77 -9.35 25 210665_at TFPI -9.20 2.00E-16 2.72E-13 -0.75 -9.33 2q31- q32.1 26 227680_at LOC284695 -2.04 5.14E-15 4.67E-12 -0.76 -9.20 1p22.1 27 221235_s_at -2.05 4.09E-16 4.91 E-13 -0.72 -9.11 28 228974_at -3.16 3.51E-16 4.39E-13 -0.71 -9.10 29 226508_at -1.73 1.54E-15 1.71 E-12 -0.71 -8.94 30 225223_at -2.15 8.69E-15 6.68E-12 -0.72 -8.90 31 244103_at -2.08 2.99E-14 1.91 E-11 -0.73 -8.88 32 213549_at PRO2730 -2.68 1.66E-15 1.77E-12 -0.69 -8.85 3p21.31 33 226867_at FLJ20686 -2.48 1.53E-15 1.71 E-12 -0.69 -8.85 9p21.3 34 233849_s_at ARHGAP5 -6.23 2.02E-15 2.02E-12 -0.69 -8.81 14q12 35 208116_s_at MAN1A1 -2.89 6.12E-15 5.12E-12 -0.70 -8.79 6q22 36 232979_at -3.41 2.76E-15 2.67E-12 -0.69 -8.76 37 243888_at -2.66 5.90E-15 5.12E-12 -0.70 -8.76 38 223298_s_at NT5C3 -1.70 3.69E-15 3.46E-12 -0.69 -8.76 7p14.3 39 230743_at -2.09 1.03E-14 7.76E-12 -0.70 -8.75 40 219094_at HSPC056 -2.10 1.34E-14 9.64E-12 -0.71 -8.75 3q22.3 46 i abiei+2 41 229519_at FXR1 -2.12 1.35E-14 9.64E-12 -0.70 -8.71 3q28 42 203544_s_at STAM -2.56 1.71E-14 1.17E-11 -0.70 -8.68 10p14- p13 43 227259_at CD47 -1.62 2.50E-13 1.27E-10 -0.73 -8.63 3q13.1- q13.2 44 221760_at MA 1A1 -3.82 6.14E-15 5.12E-12 -0.68 -8.62 6q22 45 231870_s_at CGI-07 -1.64 1.76E-12 6.07E-10 -0.76 -8.60 3q26.1 46 236251_at -3.32 1.66E-14 1.16E-11 -0.68 -8.59 47 236198_at -5.13 7.84E-15 6.36E-12 -0.67 -8.58 48 201242_s_at ATP1B1 -3.70 1.88E-14 1.25E-11 -0.68 -8.58 1q22-q25 49 225406_at TWSG1 -2.25 1.18E-12 4.41 E-10 -0.74 -8.55 18p11.3 50 204951 at ARHH -3.11 4.67E-14 2.86E-11 -0.68 -8.48 4p13
2.4 11q23 versus t(15;17)
# affy id HUGO name fc p q stn t Map Location 1 221004_s_at ITM2C -11.20 1.59E-14 7.61 E-11 -2.87 -17.09 2q37 2 38487_at STAB1 -16.01 3.30E-13 5.91 E-10 -2.90 -16.10 3p21.31 3 203948_s_at MPO -6.05 4.56E-20 1.14E-15 -2.14 -15.28 17q23.1 4 205624_at CPA3 -35.38 6.12E-12 5.68E-09 -3.00 -14.74 3q21-q25 5 212953_x_at CALR -3.21 1.82E-14 7.61 E-11 -2.20 -14.27 19p13.3- p13.2 6 214450_at CTSW -6.21 4.49E-14 1.36E-10 -2.19 -14.03 11q13.1 7 200953_s_at CCND2 -6.31 2.30E-12 2.80E-09 -2.26 -13.45 12p13 8 214651_s_at HOXA9 234.13 3.24E-14 1.16E-10 2.39 13.42 7p15-p14 9 203949_at MPO -4.22 1.85E-17 2.31 E-13 -1.87 -13.25 17q23.1 10 238022_at -6.27 2.35E-12 2.80E-09 -1.99 -12.44 11 206871 _at ELA2 -4.10 1.64E-16 1.37E-12 -1.75 -12.43 19p13.3 12 233072_at KIAA1857 -12.50 6.74E-11 3.12E-08 -2.26 -12.31 9q34 13 213147_at HOXA10 23.75 2.86E-13 5.88E-10 2.04 12.19 7p15-p14 14 201029_s_at CD99 -2.27 1.40E-15 8.79E-12 -1.62 -11.54 Xp22.32 15 204150_at STAB1 -19.83 3.61 E-10 1.14E-07 -2.25 -11.52 3p21.31 16 206847_s_at HOXA7 9.16 4.76E-13 7.95E-10 1.78 11.45 7p15-p14 17 210788_s_at retSDR4 -2.58 1.11 E-11 8.39E-09 -1.79 -11.35 14q22.3 18 209448_at HTATIP2 10.11 1.01 E-12 1.58E-09 1.80 11.31 11p15.1 19 200951_s_at CCND2 -7.13 1.97E-10 7.68E-08 -1.93 -11.10 12p13 20 205663_at PCBP3 -3.88 3.71 E-11 1.90E-08 -1.79 -11.09 21 q22.3 21 212509_s_at -6.33 1.39E-10 6.21 E-08 -1.87 -11.03 22 206761_at TACTILE -25.65 1.23E-09 2.84E-07 -2.20 -10.83 3q13.13 23 235753_at 16.24 7.41 E-12 6.19E-09 1.86 10.77 24 231736_x_at MGST1 -2.95 1.27E-13 2.89E-10 -1.53 -10.74 12p12.3- p12.1 25 213587_s_at LOC155066 7.68 8.23E-12 6.65E-09 1.74 10.58 7q36.1 26 224918_x_at MGST1 -2.77 4.90E-14 1.36E-10 -1.49 -10.57 12p12.3- p12.1 27 201596_x_at KRT18 -9.08 5.27E-10 1.50E-07 -1.81 -10.49 12q13 28 205349_at GNA15 -3.93 1.96E-12 2.73E-09 -1.53 -10.47 19p13.3 29 217848_s_at PP 3.79 3.05E-13 5.88E-10 1.50 10.44 10q11.1- q24 47 Table1+2 30 201522_x_at SNRPN 4.60 7.40E-14 1.85E-10 1.46 10.39 15q12 31 205771_s_at AKAP7 9.76 6.69E-12 5.78E-09 1.62 10.38 6q23 32 200952_s_at CCND2 -3.93 2.46E-10 8.91 E-08 -1.67 -10.25 12p13 33 225532_at LOC91768 -5.23 7.13E-10 1.88E-07 -1.73 -10.17 18q11.1 34 225386_s_at LOC92906 35.64 2.81 E-11 1.67E-08 1.73 10.16 2p22.2 35 221253_s_at MGC3178 -3.09 1.65E-10 7.12E-08 -1.61 -10.14 6p24.3 36 218404_at SNX10 6.55 1.28E-11 9.41 E-09 1.55 10.03 7p15.2 37 204425_at ARHGAP4 15.70 3.11 E-11 1.80E-08 1.63 9.99 Xq28 38 204082_at PBX3 8.58 2.56E-11 1.66E-08 1.58 9.93 9q33-q34 39 209905_at H0XA9 701.37 6.10E-11 2.94E-08 1.77 9.88 7p15-p14 40 217716_s_at SEC61A1 -1.97 6.02E-12 5.68E-09 -1.43 -9.86 3q21.3 41 213571_s_at EIF4EL3 2.56 1.14E-12 1.67E-09 1.41 9.85 2q37.1 42 225570_at SLC41A1 3.46 2.26E-12 2.80E-09 1.41 9.81 1q32.1 43 223663_at FLJ37970 7.30 4.86E-12 5.07E-09 1.41 9.71 11q12.3 44 241383_at -4.20 3.65E-09 6.44E-07 -1.74 -9.68 45 219837_s_at C17 -67.10 8.83E-09 1.18E-06 -2.02 -9.65 4p16-p15 46 210140_at CST7 -6.71 1.39E-09 3.08E-07 -1.61 -9.65 20p11.21 47 208852_s_at CANX -2.25 6.37E-11 3.01 E-08 -1.43 -9.58 5q35 48 216417_x_at H0XB9 3.56 4.25E-12 4.63E-09 1.38 9.57 17q21.3 49 212813_at JAM3 -4.92 4.22E-09 7.05E-07 -1.69 -9.54 11q25 50 202746 at ITM2A -18.16 8.43E-09 1.14E-06 -1.85 -9.52 Xq13.3- Xq21.2
2.5 11q23 versus t(8;21)
# affy id HUGO name fc p q stn t Map Location 1 214651_s_at HOXA9 206.03 3.28E-14 1.03E-09 2.38 13.41 7p15-p14 2 221581_s_at WBSCR5 9.58 9.94E-14 1.56E-09 1.98 12.37 7q11.23 3 213147_at HOXA10 15.43 4.12E-13 3.22E-09 1.91 11.80 7p15-p14 4 206847_s_at HOXA7 8.17 9.28E-13 5.26E-09 1.83 11.41 7p15-p14 5 235753_at 14.64 8.54E-12 2.97E-08 1.82 10.68 6 201105_at LGALS1 6.65 1.61 E-12 7.21 E-09 1.54 10.34 22q13.1 7 227853_at 3.55 1.68E-13 1.76E-09 1.47 10.30 8 209905_at HOXA9 614.03 6.13E-11 1.37E-07 1.77 9.87 7p15-p14 9 203949_at MPO -3.89 1.01 E-12 5.26E-09 -1.40 -9.82 17q23.1 10 210314_x_at TNFSF13 4.55 4.40E-12 1.72E-08 1.42 9.72 17p13.1 11 213908_at 15.54 1.15E-10 2.13E-07 1.61 9.55 12 213150_at HOXA10 54.55 2.66E-10 3.78E-07 1.61 9.25 7p15-p14 13 209500_x_at TNFSF13 3.85 4.68E-11 1.22E-07 1.37 9.17 17p13.1 14 204082_at PBX3 6.31 5.89E-11 1.37E-07 1.34 9.03 9q33-q34 15 205639_at AOAH 5.46 8.40E-11 1.75E-07 1.29 8.80 7p14-p12 16 228365_at LOC144402 7.86 5.32E-10 6.36E-07 1.42 8.80 12q11 17 208890_s_at PLXNB2 3.97 9.29E-11 1.82E-07 1.29 8.76 22q13.33 18 228083_at CACNA2D4 12.54 7.21 E-10 7.06E-07 1.44 8.75 12p13.33 19 201944_at HEXB 3.38 5.49E-10 6.36E-07 1.39 8.72 5q13 20 218404_at SNX10 4.18 1.56E-10 2.65E-07 1.29 8.68 7p15.2 21 204202_at KIAA1023 3.42 1.65E-10 2.65E-07 1.28 8.66 7p22.3 48 Table1+2 22 225245_x_at H2AFJ 4.99 2.65E-10 3.78E-07 1.30 8.64 12p12 23 212459_x_at SUCLG2 3.67 2.89E-11 9.04E-08 1.22 8.63 3p14.2 24 216417_x_at HOXB9 3.30 4.27E-11 1.22E-07 1.21 8.51 17q21.3 25 223562_at PARVG 3.18 5.28E-10 6.36E-07 1.25 8.36 22q13.2- q13 26 218217_at RISC 5.15 1.01 E-09 8.75E-07 1.29 8.35 17q23.1 27 203948_s_at MPO -4.44 6.12E-10 6.61 E-07 -1.23 -8.34 17q23.1 28 228058_at LOC124220 -6.10 5.49E-09 3.37E-06 -1.29 -8.28 16p13.3 29 241706_at LOC144402 5.35 8.09E-10 7.45E-07 1.22 8.17 12q11 30 201850_at CAPG 7.89 3.15E-09 2.10E-06 1.35 8.17 2cen-q24 31 224301_x_at H2AFJ 4.16 7.21 E-10 7.06E-07 1.21 8.17 12p12 32 214835_s_at SUCLG2 3.91 4.04E-10 5.27E-07 1.19 8.16 3p14.2 33 206940_s_at POU4F1 -33.65 1.84E-07 3.22E-05 -1.76 -8.14 13q21.1- q22 34 212423_at FLJ90798 5.61 1.08E-09 9.14E-07 1.22 8.14 10q22.3 35 215772_x_at SUCLG2 3.87 1.69E-10 2.65E-07 1.15 8.09 3p14.2 36 202746_at ITM2A -7.27 5.70E-08 1.67E-05 -1.39 -8.08 Xq13.3- Xq21.2 37 238756_at 4.09 1.20E-09 9.93E-07 1.21 8.08 38 204880_at MGMT -2.32 5.45E-09 3.37E-06 -1.23 -8.04 10q26 39 241370_at 3.17 2.09E-09 1.49E-06 1.20 7.94 40 224415_s_at HINT2 2.05 3.49E-10 4.75E-07 1.13 7.93 9p13.1 41 228827_at - 2.83E-07 4.30E-05 -1.80 -7.92 103.62 42 225386_s_at LOC92906 6.59 6.59E-10 6.88E-07 1.14 7.90 2p22.2 43 200788_s_at PEA15 2.38 7.77E-10 7.37E-07 1.14 7.87 1q21.1 44 207839_s_at LOC51754 2.68 5.92E-10 6.61 E-07 1.12 7.85 9p13.1 45 206009_at ITGA9 -3.62 5.12E-08 1.58E-05 -1.28 -7.81 3p21.3 46 211341_at POU4F1 - 3.58E-07 5.05E-05 -1.74 -7.79 13q21.1- 150.84 q22 47 56256_at CGI-40 2.81 1.88E-09 1.37E-06 1.14 7.77 11q23.3 48 217520_x_at LOC283683 16.90 1.17E-08 5.50E-06 1.38 7.76 15q11.2 49 219478_at WFDC1 -6.75 1.65E-07 3.09E-05 -1.36 -7.72 16q24.3 50 205774_at F12 3.18 1.69E-09 1.32E-06 1.11 7.68 5q33-qter
2.6 inv(16) versus inv(3)
# affy id HUGO name fc stn t Map Location 1 203949_at MPO 4.74 1.72E-13 4.54E-09 2.41 14.22 17q23.1 2 203948_s_at MPO 5.13 2.36E-12 2.08E-08 1.89 11.46 17q23.1 3 205382_s_at DF 5.65 1.05E-12 1.38E-08 1.83 11.19 19p13.3 4 201497_x_at MYH11 18.46 2.05E-10 7.07E-07 2.06 10.65 16p13.13- p13.12 5 224841_x_at -1.69 2.14E-10 7.07E-07 -1.76 -10.33 6 224741_x_at -1.69 3.09E-10 9.08E-07 -1.76 -10.28 7 209365_s_at ECM1 3.28 3.37E-11 2.23E-07 1.54 9.53 1q21 8 210755_at HGF 6.18 6.96E-10 1.84E-06 1.65 9.44 7q21.1 9 228497_at FL1PT1 -3.11 8.82E-09 1.17E-05 -1.63 -9.19 1p13.1 10 205718 at ITGB7 3.07 1.91 E-10 7.07E-07 1.44 8.88 12q13.13 49 Table1+2 11 205131_x_at SCGF 4.37 1.79E-10 7.07E-07 1.40 8.73 19q13.3 12 217963_s_at NGFRAP1 -20.39 5.19E-07 1.67E-04 -1.88 -8.49 Xq22.1 13 201496_x_at MYH11 3.64 1.43E-09 3.16E-06 1.40 8.45 16p13.13- P13.12 14 222862_s_at AK5 40.65 3.10E-08 2.93E-05 1.61 8.14 1p31 15 236646_at FLJ31166 3.02 9.63E-10 2.31 E-06 1.30 8.12 12p13.31 16 226197_at 2.75 2.51 E-09 4.46E-06 1.31 8.04 17 203074_at ANXA8 1.80 2.08E-09 4.22E-06 1.30 8.04 10q11.2 18 243244_at 3.90 2.53E-09 4.46E-06 1.29 7.95 19 202605_at GUSB 2.22 4.26E-08 3.47E-05 1.30 7.70 7q21.11 20 212358_at CLlPR-59 15.49 8.58E-08 5.04E-05 1.46 7.63 19q13.12 21 201360_at CST3 3.63 4.80E-09 7.94E-06 1.22 7.62 20p11.21 22 226697_at LOC92689 2.52 6.69E-09 1.04E-05 1.22 7.58 4p14 23 201462_at KIAA0193 -5.29 3.06E-07 1.13E-04 -1.37 -7.57 7p14.3- p14.1 24 241525_at LOC200772 55.36 1.35E-07 6.48E-05 1.47 7.46 2q37.3 25 210783_x_at SCGF 4.12 8.13E-09 1.13E-05 1.20 7.46 19q13.3 26 231736_x_at MGST1 3.57 7.41 E-09 1.09E-05 1.19 7.44 12p12.3- p12.1 27 207961_x_at MYH11 15.00 1.40E-07 6.63E-05 1.43 7.42 16p13.13- p13.12 28 224441_s_at MGC14793 -3.13 8.20E-08 5.04E-05 -1.24 -7.37 6q16.3 29 205076_s_at CRA 4.21 4.89E-08 3.77E-05 1.24 7.34 1q12-q21 30 210997_at HGF 17.75 1.55E-07 6.94E-05 1.38 7.34 7q21.1 31 209975_at CYP2E1 3.46 4.33E-08 3.47E-05 1.22 7.30 10q24.3- qter 32 224918_x_at MGST1 3.27 1.58E-08 1.90E-05 1.18 7.29 12p12.3- p12.1 33 201069_at MMP2 2.83 1.26E-08 1.59E-05 1.17 7.28 16q13- q21 34 202828_s_at MMP14 5.47 1.26E-07 6.34E-05 1.29 7.25 14q11- q12 35 211709_s_at SCGF 3.22 3.48E-08 3.08E-05 1.18 7.24 19q13.3 36 202283_at SERP1NF1 4.68 3.61 E-08 3.08E-05 1.18 7.18 17p13.1 37 200852_x_at GNB2 2.10 2.31 E-08 2.65E-05 1.15 7.16 7q22 38 201688_s_at TPD52 -3.31 7.77E-07 2.23E-04 -1.30 -7.14 8q21 39 219308_s_at AK5 5.75 2.20E-07 9.06E-05 1.32 7.14 1p31 40 239814_at 2.34 2.50E-08 2.75E-05 1.14 7.12 41 200985_s_at CD59 -6.95 2.61 E-06 5.15E-04 -1.42 -7.09 11p13 42 242621_at FLJ32468 1.47 2.87E-08 2.81 E-05 1.14 7.08 7q22.1 43 202185_at PL0D3 1.78 2.78E-08 2.81 E-05 1.14 7.07 7q22 44 223136_at AIG-1 -5.06 9.07E-07 2.45E-04 -1.28 -7.05 6q24.1 45 223091_x_at GL004 -1.53 1.27E-07 6.34E-05 -1.17 -7.04 2q36.3 46 223354_x_at GL004 -1.62 2.88E-07 1.09E-04 -1.21 -7.04 2q36.3 47 214797_s_at PCTK3 -2.39 4.15E-07 1.44E-04 -1.22 -7.03 1q31-q32 48 214558_at GPR12 1.53 4.99E-08 3.77E-05 1.14 7.01 13q12 49 229309_at 4.49 6.27E-08 4.25E-05 1.15 7.01 50 205859_at LY86 3.30 2.78E-08 2.81 E-05 1.12 7.01 6p24.3
2.7 inv(16) versus normal affy id HUGO name fc p q stn t Map Location 1 214651_s_at HOXA9 -17.28 4.68E-43 1.11E-38 -1.58 -19.65 7p15-p14 2 235753_at -9.51 1.52E-37 1.81E-33 -1.46 -17.75 3 202370_s_at CBFB -2.85 2.71 E-34 1.74E-30 -1.34 -16.58 16q22.1 4 209905_at HOXA9 -49.46 2.93E-34 1.74E-30 -1.38 -16.55 7p15-p14 5 225055_at DKFZp667M2411 -4.74 9.40E-32 3.72E-28 -1.31 -16.01 17q11.2 6 206847_s_at HOXA7 -5.34 1.82E-33 8.62E-30 -1.26 -15.70 7p15-p14 7 227567_at -4.87 2.00E-31 6.78E-28 -1.28 -15.69 8 213150_at HOXA10 -8.11 2.51 E-31 7.45E-28 -1.19 -14.82 7p15-p14 9 213737_x_at -2.49 2.13E-30 5.62E-27 -1.18 -14.69
10 213147_at HOXA10 -4.48 8.29E-26 8.20E-23 -1.20 -14.29 7p15-p14
11 235521_at HOXA3 -15.59 1.02E-28 2.20E-25 -1.17 -14.19 7p15-p14
12 226352_at -5.92 1.71E-29 4.05E-26 -1.13 -14.10
13 209406_at BAG2 -4.42 1.16E-28 2.30E-25 -1.11 -13.82 6p12.3- p11.2
14 213353_at ABCA5 -3.50 6.04E-22 2.87E-19 -1.17 -13.54 17q24.3
15 205600_x_at HOXB5 -2.61 7.86E-27 1.11E-23 -1.09 -13.48 17q21.3
16 232636_at DKFZp547M2010 -10.69 7.96E-27 1.11E-23 -1.11 -13.44 Xq27.3
17 222786_at C4S-2 -3.61 2.21 E-27 4.04E-24 -1.07 -13.31 7p22
18 217963_s_at NGFRAP1 -11.73 3.36E-27 5.70E-24 -1.06 -13.24 Xq22.1
19 201432_at CAT -2.19 7.17E-20 2.58E-17 -1.17 -13.16 11p13
20 219304_s_at SCDGF-B -3.85 7.59E-27 1.11 E-23 -1.06 -13.15 11q22.3
21 213844_at HOXA5 -8.27 3.64E-26 3.92E-23 -1.05 -13.03 7p15-p14
22 223044_at SLC11A3 -9.45 1.35E-26 1.78E-23 -1.04 -13.02 2q32
23 223471_at RAB3IP -3.39 5.51 E-25 4.51 E-22 -1.06 -12.99
24 219218_at FLJ23058 -6.85 2.81 E-26 3.17E-23 -1.04 -12.97 17q25.3
25 211031_s_at CYLN2 -5.90 2.18E-26 2.73E-23 -1.04 -12.95 7q11.23
26 227224_at FLJ25604 -5.22 1.47E-25 1.40E-22 -1.05 -12.93 1q24.2
27 230894_s_at -11.16 2.66E-26 3.16E-23 -1.03 -12.91
28 213908_at -5.06 5.26E-26 5.42E-23 -1.04 -12.89
29 233467_s_at PHEMX -1.84 1.87E-22 1.08E-19 -1.09 -12.89 11p15.5
30 229194_at -2.74 1.68E-21 7.27E-19 -1.08 -12.73
31 205366_s_at HOXB6 -15.94 8.94E-25 6.85E-22 -1.05 -12.68 17q21.3
32 239791_at -20.64 1.19E-24 8.86E-22 -1.06 -12.67
33 235749_at UGCGL2 -6.39 2.73E-25 2.49E-22 -1.00 -12.54 13q32.1
34 224952_at DKFZP564D166 -3.67 1.66E-20 6.80E-18 -1.08 -12.51 17q23.3
35 225102_at LOC 152009 -4.87 4.14E-25 3.64E-22 -1.00 -12.50 3q21.3
36 236892_s_at -16.62 4.37E-24 3.14E-21 -1.05 -12.46
37 205601_s_at HOXB5 -3.18 5.93E-25 4.69E-22 -1.00 -12.45 17q21.3
38 241706_at LOC 144402 -6.05 5.40E-25 4.51 E-22 -1.00 -12.44 12q11
39 218414_s_at NUDE1 -2.08 1.24E-23 8.66E-21 -1.01 -12.43 16p13.11
40 218477_at PTD011 -2.94 1.42E-22 8.62E-20 -0.99 -12.08 6p12.1
41 201669_s_at MARCKS -12.15 1.50E-23 1.02E-20 -0.98 -12.08 6q22.2
42 235391_at LOC137392 -9.70 2.13E-23 1.41 E-20 -0.98 -12.04 8q21.3
43 200675_at CD81 -3.09 1.41 E-18 4.09E-16 -1.05 -12.00 11p15.5
44 231310_at 3.38 9.97E-13 1.11E-10 1.42 11.97
45 213779_at LOC 129080 -2.87 2.71 E-22 1.42E-19 -0.98 -11.93 22q12.1 51 Table1+2 46 203949_at MPO 2.10 4.63E-20 1.72E-17 1.01 11.91 17q23.1 47 228904_at -5.66 3.84E-23 2.47E-20 -0.97 -11.89 48 241985_at FLJ37870 -6.15 5.95E-23 3.72E-20 -0.94 -11.70 5q13.3 49 200665_s_at SPARC 5.30 4.17E-12 4.17E-10 1.45 11.63 5q31.3- q32 50 200984_s_at CD59 -3.57 1.83E-22 1.08E-19 -0.93 -11.54 11p13
2.8 inv(16) versus t(15;17) affy id HUGO name fc p q stn t Map Location 1 211990_at HLA-DPA1 12.88 7.26E-18 1.92E-13 3.35 20.08 6p21.3 2 214450_at CTSW -8.03 6.77E-13 7.14E-10 -3.05 -15.96 11q13.1 3 38487_at STAB1 -8.03 2.37E-12 1.95E-09 -3.01 -15.25 3p21.31 4 221004_s_at ITM2C -5.22 1.41 E-13 3.01 E-10 -2.58 -15.04 2q37 5 204661_at CDW52 33.75 1.67E-13 3.15E-10 2.69 14.74 1p36 6 200654_at P4HB -2.30 1.92E-15 1.27E-11 -2.31 -14.63 17q25 7 203535_at S100A9 9.01 7.53E-16 6.62E-12 2.24 14.32 1q21 8 217478_s_at HLA-DMA 7.63 2.80E-14 8.72E-11 2.35 14.21 6p21.3 9 209732_at CLECSF2 30.47 5.76E-13 6.61 E-10 2.71 14.20 12p13- p12 10 34210_at CDW52 43.85 7.27E-13 7.14E-10 2.58 13.90 1p36 11 238022_at -8.74 2.99E-12 2.25E-09 -2.41 -13.63 12 209619_at CD74 5.65 3.24E-16 4.28E-12 2.06 13.52 5q32 13 201923_at PRDX4 7.22 7.48E-14 1.79E-10 2.16 13.28 Xp22.13 14 205624_at CPA3 -9.54 1.00E-11 6.01 E-09 -2.41 -13.24 3q21-q25 15 204563_at SELL 9.35 7.30E-13 7.14E-10 2.25 13.07 1q23-q25 16 200931_s_at VCL 3.96 1.06E-14 5.62E-11 2.01 12.90 10q22.1- q23 17 231310_at 4.74 2.97E-14 8.72E-11 2.04 12.89 18 209312_x_at HLA-DRB1 8.89 3.15E-13 4.37E-10 2.06 12.62 6p21.3 19 208306_x_at HLA-DRB4 9.65 5.23E-13 6.43E-10 2.08 12.60 6p21.3 20 238365_s_at -10.74 1.01 E-10 3.36E-08 -2.50 -12.45 21 208891_at DUSP6 7.70 2.11 E-14 8.72E-11 1.93 12.44 12q22- q23 22 212953_x_at CALR -2.84 2.97E-14 8.72E-11 -1.91 -12.34 19p13.3- p13.2 23 204670_x_at HLA-DRB5 6.79 3.94E-14 1.04E-10 1.91 12.25 6p21.3 24 205718_at ITGB7 6.61 6.63E-13 7.14E-10 1.97 12.10 12q13.13 25 205453_at HOXB2 11.16 1.03E-11 6.03E-09 2.13 11.95 17q21- q22 26 205663_at PCBP3 -4.69 1.37E-11 7.52E-09 -2.01 -11.85 21q22.3 27 232617_at CTSS 8.88 1.90E-11 9.29E-09 2.15 11.78 1q21 28 207375_s_at IL15RA 4.80 1.48E-13 3.01 E-10 1.84 11.77 10p15- p14 29 224583_at COTL1 5.58 3.11 E-13 4.37E-10 1.86 11.77 16q23.3 30 221059_s_at CHST6 6.80 4.13E-12 2.80E-09 1.95 11.67 16q22 31 233072_at KIAA1857 -7.47 2.04E-10 5.49E-08 -2.19 -11.60 9q34 32 229168_at DKFZp434K0621 -6.73 3.74E-10 8.88E-08 -2.36 -11.59 5q35.3 33 208982_at PECAM1 4.84 2.17E-12 1.85E-09 1.88 11.55 17q23 52 Ta e + 34 224839_s_at GPT2 -9.02 4.23E-11 1.75E-08 -1.95 -11.41 16q12.1 35 202803_s_at 1TGB2 5.43 5.36E-13 6.43E-10 1.72 11.07 21 q22.3 36 223280_x_at MS4A6A 24.98 9.94E-11 3.36E-08 2.11 11.04 11q12.1 37 201496_x_at MYH11 10.61 1.13E-11 6.47E-09 1.81 10.98 16p13.13- p13.12 38 211991_s_at HLA-DPA1 25.17 9.82E-11 3.36E-08 2.05 10.97 6p21.3 39 204150_at STAB1 -9.71 1.08E-09 2.11 E-07 -2.26 -10.94 3p21.31 40 208689_s_at RPN2 -1.75 1.91 E-13 3.36E-10 -1.66 -10.90 20q12- q13.1 41 220798_x_at FLJ 11535 -3.81 7.69E-11 2.82E-08 -1.84 -10.89 19p13.3 42 201497_x_at MYH11 28.44 1.48E-10 4.48E-08 2.16 10.88 16p13.13- p13.12 43 202917_s_at S100A8 3.19 3.79E-13 5.01 E-10 1.66 10.85 1q21 44 241742_at PRAM-1 11.60 1.23E-10 3.81 E-08 1.97 10.76 19p13.2 45 228046_at LOC 152485 3.03 5.49E-12 3.54E-09 1.72 10.76 4q31.1 46 226878_at 4.19 1.90E-11 9.29E-09 1.77 10.75 47 238604_at 3.63 2.30E-13 3.79E-10 1.62 10.71 48 213779_at LOC 129080 -6.64 9.66E-10 1.96E-07 -2.04 -10.68 22q12.1 49 224356_x_at MS4A6A 25.23 2.22E-10 5.74E-08 2.06 10.62 11q12.1 50 217897 at FXYD6 3.03 3.34E-11 1.44E-08 1.77 10.62 11q23.3
2.9 inv(16) versus t(8;21) affy id HUGO name fc p q stn t Map Location 1 207075_at CIAS1 6.59 1.58E-12 1.75E-08 2.20 12.68 1q44 2 208890_s_at PLXNB2 5.12 3.17E-13 7.15E-09 1.97 12.18 22q13.33 3 205453_at HOXB2 12.87 7.80E-12 3.24E-08 2.16 12.11 17q21- q22 4 205419_at EBI2 7.52 3.29E-12 2.73E-08 2.01 11.90 13q32.2 5 205718_at ITGB7 6.71 4.31E-13 7.15E-09 1.91 11.89 12q13.13 6 224764_at ARHGAP10 8.78 1.26E-11 4.63E-08 2.02 11.59 10 7 201497_x_at MYH11 26.12 1.56E-10 2.16E-07 2.14 10.85 16p13.13- p13.12 8 201496_x_at MYH11 9.21 1.72E-11 5.70E-08 1.80 10.83 16p13.13- P13.12 9 224049_at KCNK17 4.64 1.11 E-10 1.77E-07 1.92 10.69 6p21.1 10 200665_s_at SPARC 4.28 7.71 E-12 3.24E-08 1.63 10.32 5q31.3- q32 11 224724_at SULF2 26.61 4.15E-10 4.05E-07 1.99 10.28 20q 12- 13.2 12 218236_s_at PRKCN 4.73 5.10E-12 3.10E-08 1.59 10.16 2p21 13 218795_at ACP6 -4.42 3.10E-10 3.26E-07 -1.68 -10.03 1q21 14 201425_at ALDH2 7.98 2.08E-10 2.50E-07 1.72 10.03 12q24.2 15 201944_at HEXB 2.26 4.28E-11 1.01 E-07 1.57 9.82 5q13 16 201887_at IL13RA1 4.99 3.14E-10 3.26E-07 1.63 9.67 Xq24 17 201360_at CST3 5.36 1.21 E-10 1.83E-07 1.57 9.65 20p11.21 18 238604_at 3.10 5.61E-12 3.10E-08 1.46 9.56 19 209365_s_at ECM1 3.14 3.60E-11 9.96E-08 1.49 9.52 1q21 20 201596_x_at KRT18 7.58 2.11E-10 2.50E-07 1.56 9.52 12q13 21 202670_at MAP2K1 3.60 5.03E-10 4.58E-07 1.59 9.45 15q22.1- 53 Table1+2 q22.33 22 203320_at LNK 3.09 1.34E-10 1.94E-07 1.50 9.37 12q24 23 210314_x_at TNFSF13 4.88 2.77E-10 3.06E-07 1.53 9.36 17p13.1 24 209500_x_at TNFSF13 4.05 4.42E-10 4.19E-07 1.55 9.34 17p13.1 25 221841_s_at 4.04 3.60E-11 9.96E-08 1.42 9.21 26 235359_at 2.91 1.88E-10 2.49E-07 1.47 9.20 27 223249_at CLDN12 3.53 1.06E-10 1.77E-07 1.44 9.16 7q21 28 218217_at RISC 3.35 1.12E-10 1.77E-07 1.43 9.10 17q23.1 29 201739_at SGK 4.42 4.17E-11 1.01 E-07 1.40 9.07 6q23 30 229309_at 11.50 3.64E-09 1.89E-06 1.64 9.01 31 240572_s_at 3.26 9.26E-11 1.77E-07 1.39 8.95 32 208683_at CAPN2 3.21 9.71 E-11 1.77E-07 1.38 8.92 1q41-q42 33 225602_at C9orf19 2.86 5.10E-11 1.13E-07 1.36 8.90 9p13-p12 34 226818_at LOC219972 11.01 2.61 E-09 1.63E-06 1.54 8.89 11q12.1 35 220974_x_at BA108L7.2 4.78 3.85E-10 3.87E-07 1.39 8.79 10q24.31 36 229383_at 5.01 3.55E-09 1.87E-06 1.52 8.77 37 212459_x_at SUCLG2 3.54 8.98E-11 1.77E-07 1.34 8.72 3p14.2 38 205859_at LY86 3.60 1.34E-09 1.01 E-06 1.43 8.71 6p24.3 39 211084_x_at PRKCN 4.82 2.26E-10 2.58E-07 1.33 8.60 2p21 40 236738_at 6.52 1.66E-09 1.20E-06 1.40 8.60 41 217849_s_at CDC42BPB 4.85 2.02E-10 2.50E-07 1.32 8.59 14q32.3 42 205330_at MN1 9.06 1.06E-08 4.35E-06 1.56 8.52 22q12.1 43 204057_at ICSBP1 4.27 5.50E-09 2.68E-06 1.44 8.46 16q24.1 44 228415_at AP1S2 2.82 2.29E-09 1.52E-06 1.33 8.30 Xp22.31 45 202283_at SERPINF1 8.45 2.79E-09 1.65E-06 1.34 8.29 17p13.1 46 226841_at LOC219972 12.54 1.86E-08 6.29E-06 1.51 8.26 11q12.1 47 226137_at 3.27 4.82E-09 2.42E-06 1.36 8.26 48 208033_s_at ATBF1 3.76 1.34E-09 1.01 E-06 1.30 8.24 16q22.3- q23.1 49 233555_s_at SULF2 17.48 2.64E-08 8.12E-06 1.58 8.19 20q12- 13.2 50 205076_s_at CRA 5.49 1.56E-08 5.96E-06 1.44 8.19 1q12-q21
2.10 inv(3) versus normal affy id HUGO name fc p q i stn t Map Location 1 205382_s_at DF -5.23 7.94E-22 5.04E-18 -1.05 -12.36 19p13.3 2 236892_s_at -12.75 1.92E-23 4.88E-19 -1.02 -12.16 3 239791_at -11.42 4.78E-23 6.07E-19 -0.99 -11.89 4 213844_at HOXA5 -6.53 5.98E-20 2.53E-16 -1.01 -11.81 7p15-p14 5 213110_s_at COL4A5 -16.77 4.56E-22 3.85E-18 -0.98 -11.63 Xq22 6 204082_at PBX3 -4.66 3.88E-21 1.97E-17 -0.97 -11.52 9q33-q34 7 230480_at HIWI2 -3.42 1.85E-19 6.72E-16 -0.92 -10.96 11 q21 8 228904_at -5.19 2.38E-19 7.54E-16 -0.89 -10.67 9 204301_at KIAA0711 -4.92 4.74E-19 1.34E-15 -0.89 -10.63 8p23.2 10 219304_s_at SCDGF-B -3.13 1.23E-16 2.60E-13 -0.89 -10.33 11 q22.3 11 230743 at -2.36 2.58E-17 5.95E-14 -0.88 -10.31 54 l abieι+2 12 205767_at EREG -8.84 2.69E-18 6.83E-15 -0.83 -10.03 4q21.1 13 213893_x_at PMS2L5 -1.96 9.34E-11 4.65E-08 -1.02 -9.84 7q11-q22 14 235753_at -3.36 5.47E-13 5.78E-10 -0.91 -9.81 15 226789_at -2.42 2.56E-13 3.24E-10 -0.90 -9.77 16 241464_s_at -2.58 2.70E-15 4.89E-12 -0.84 -9.66 17 226556_at -2.94 1.47E-12 1.29E-09 -0.90 -9.59 18 205600_x_at HOXB5 -2.09 5.29E-13 5.78E-10 -0.88 -9.55 17q21.3 19 212318_at TRN-SR -2.02 1.62E-10 6.76E-08 -0.97 -9.47 7q32.2 20 204548_at STAR -4.50 5.21 E-15 8.82E-12 -0.80 -9.36 8p11.2 21 204647_at HOMER3 -4.86 2.10E-16 4.10E-13 -0.77 -9.35 19p13.11 22 240151_at -2.60 1.42E-11 9.03E-09 -0.88 -9.25 23 231300_at LOC90835 -2.58 7.77E-12 5.48E-09 -0.86 -9.19 16p11.2 24 209905_at HOXA9 -4.19 8.92E-12 5.96E-09 -0.83 -8.97 7p15-p14 25 223703_at CDA017 -2.44 3.19E-13 3.85E-10 -0.79 -8.94 10q23.1 26 217499_x_at -1.62 2.41 E-13 3.24E-10 -0.78 -8.89 27 212953_x_at CALR -1.58 4.78E-11 2.58E-08 -0.82 -8.71 19p13.3- p13.2 28 236398_s_at -3.64 6.70E-11 3.54E-08 -0.82 -8.64 29 210006_at DKFZP5640243 -1.73 1.60E-11 9.88E-09 -0.78 -8.56 3p21.1 30 205624_at CPA3 -6.67 1.90E-14 3.02E-11 -0.70 -8.52 3q21-q25 31 203746_s_at HCCS -1.55 4.25E-14 6.35E-11 -0.71 -8.49 Xp22.3 32 201186_at LRPAP1 -2.64 2.54E-13 3.24E-10 -0.72 -8.45 4p16.3 33 213292_s_at SNX13 -1.77 7.96E-10 2.43E-07 -0.82 -8.30 7p21.1 34 231175_at FLJ30162 -6.23 9.91 E-13 9.32E-10 -0.70 -8.20 6p11.1 35 212820_at RC3 -2.87 1.13E-12 1.02E-09 -0.70 -8.16 15q15.3 36 235749_at UGCGL2 -4.07 3.32E-10 1.19E-07 -0.77 -8.15 13q32.1 37 226123_at LOC286180 -2.94 1.43E-10 6.17E-08 -0.76 -8.14 8q12.1 38 232250_at KIAA1257 -3.37 9.87E-13 9.32E-10 -0.69 -8.14 3q21.3 39 214651_s_at H0XA9 -3.07 6.40E-09 1.42E-06 -0.85 -8.12 7p15-p14 40 200700_s_at KDELR2 -1.99 3.41 E-10 1.20E-07 -0.77 -8.10 7p22.2 41 210115_at RPL39L -3.91 3.47E-13 4.00E-10 -0.66 -8.01 3q27 42 239503_at -4.36 7.38E-13 7.50E-10 -0.66 -7.96 43 208967_s_at AK2 -2.18 5.27E-12 3.93E-09 -0.68 -7.94 1p34 44 205601_s_at H0XB5 -2.53 1.16E-09 3.39E-07 -0.76 -7.93 17q21.3 45 203675_at NUCB2 -2.09 7.25E-09 1.55E-06 -0.81 -7.92 11p15.1- p14 46 213150_at HOXA10 -2.71 4.92E-10 1.62E-07 -0.73 -7.81 7p15-p14 47 242621_at FLJ32468 -1.39 2.43E-10 9.34E-08 -0.71 -7.76 7q22.1 48 219551_at TRAITS -2.31 1.21 E-10 5.72E-08 -0.70 -7.76 3q13.33 49 231736_x_at MGST1 -3.01 1.93E-08 3.30E-06 -0.81 -7.75 12p12.3- p12.1 50 214575_s_at AZU1 -4.54 2.96E-11 1.71 E-08 -0.67 -7.73 19p13.3
2.11 inv(3) versus t(15;17)
# affy id HUGO name fc stn Map Location 1 212953 x at CALR -5.95 2.17E-14 5.07E-11 -3.69 -18.88 19p13.3- p13.2 55 Ta e + 2 205382_s_at DF -12.24 2.37E-15 7.12E-12 -3.43 -18.68 19p13.3 3 203948_s_at MPO -9.29 4.98E-19 1.05E-14 -3.14 -18.57 17q23.1 4 203949_at MPO -6.22 1.52E-17 1.60E-13 -3.05 -17.82 17q23.1 5 200654_at P4HB -3.78 4.67E-17 3.27E-13 -2.71 -16.03 17q25 6 214450_at CTSW -8.62 1.58E-13 2.89E-10 -2.90 -15.67 11q13.1 7 231736_x_at MGST1 -6.90 6.57E-16 2.30E-12 -2.57 -15.09 12p12.3- p12.1 8 224918_x_at MGST1 -6.02 2.58E-16 1.15E-12 -2.54 -15.02 12p12.3- p12.1 9 206871_at ELA2 -6.28 2.73E-16 1.15E-12 -2.54 -15.00 19p13.3
10 214575_s_at AZU1 -12.19 2.49E-13 3.73E-10 -2.58 -14.34 19p13.3
11 205624_at CPA3 -21.54 5.79E-12 5.79E-09 -2.85 -14.33 3q21-q25
12 208689_s_at RPN2 -2.77 3.65E-15 9.58E-12 -2.43 -14.27 20q12- q13.1
13 238022_at -8.14 1.08E-12 1.33E-09 -2.28 -12.89
14 38487_at STAB1 -5.21 5.94E-13 8.31 E-10 -2.23 -12.76 3p21.31
15 221004_s_at ITM2C -4.36 8.93E-14 1.88E-10 -2.12 -12.49 2q37
16 217716_s_at SEC61A1 -2.51 1.65E-13 2.89E-10 -2.09 -12.25 3q21.3
17 221739_at IL27w -2.24 2.31 E-13 3.73E-10 -2.06 -12.11 19p13.3
18 233072_at KIAA1857 -10.04 1.05E-10 5.14E-08 -2.37 -12.06 9q34
19 208852_s_at CANX -2.94 3.24E-12 3.78E-09 -2.07 -11.86 5q35
20 220798_x_at FLJ11535 -5.26 7.78E-12 6.81 E-09 -2.05 -11.62 19p13.3
21 217225_x_at LOC283820 -2.41 9.52E-13 1.25E-09 -1.94 -11.43 16p13.13
22 208730_x_at RAB2 2.53 8.63E-10 3.12E-07 2.18 11.42 8q12.1
23 203675_at NUCB2 -3.92 6.96E-12 6.65E-09 -2.00 -11.42 11p15.1- p14
24 201004_at SSR4 -2.77 1.64E-11 1.15E-08 -2.00 -11.33 Xq28
25 210788_s_at retSDR4 -2.65 7.69E-12 6.81 E-09 -1.95 -11.22 14q22.3
26 202759_s_at AKAP2 -4.78 2.58E-11 1.69E-08 -1.98 -11.15 9q31-q33
27 209619_at CD74 4.57 1.47E-11 1.14E-08 1.92 11.07 5q32
28 214315_x_at CALR -3.14 2.25E-11 1.52E-08 -1.93 -11.00 19p13.3- p13.2
29 229168_at DKFZp434K0621 -5.62 4.18E-10 1.72E-07 -2.12 -10.99 5q35.3
30 211990_at HLA-DPA1 12.02 1.70E-08 3.31 E-06 2.38 10.92 6p21.3
31 214797_s_at PCTK3 6.22 2.95E-09 8.48E-07 2.12 10.91 1q31-q32
32 211709_s_at SCGF -5.08 3.77E-12 3.96E-09 -1.80 -10.65 19q13.3
33 200068 s at - HG- CANX -1.76 3.59E-12 3.96E-09 -1.79 -10.61 5q35 U133A
34 206914_at CRTAM 6.82 3.01 E-09 8.54E-07 1.99 10.50 11 q22- q23
35 204897_at PTGER4 5.48 3.25E-10 1.37E-07 1.87 10.44 5p13.1
36 221253_s_at MGC3178 -3.45 5.95E-11 3.62E-08 -1.81 -10.36 6p24.3
37 225010_at D10S170 2.56 2.69E-11 1.71 E-08 1.77 10.33 10q21
38 210140_at CST7 -8.79 1.17E-09 4.09E-07 -1.98 -10.32 20p11.21
39 226905_at -1.96 8.40E-11 4.20E-08 -1.78 -10.24
40 200652_at SSR2 -1.91 1.02E-11 8.61 E-09 -1.73 -10.22 1q21-q23
41 33323_r_at SFN 1.93 1.07E-11 8.68E-09 1.73 10.21 1p35.3
42 227353_at EVER2 5.28 1.34E-08 2.75E-06 2.02 10.17 17q25.3
43 224839_s_at GPT2 -6.13 8.34E-11 4.20E-08 -1.77 -10.15 16q12.1
44 200068 s at - HG- CANX -1.67 1.62E-11 1.15E-08 -1.72 -10.14 5q35 U133B 56 a e + 45 209215_at TETRAN -3.38 1.52E-11 1.14E-08 -1.72 -10.14 4p16.3 46 205614_x_at MST1 -8.62 3.49E-09 9.53E-07 -2.00 -9.99 3p21 47 241383_at -4.56 2.13E-09 6.47E-07 -1.87 -9.85 48 214317_x_at RPS9 2.30 1.38E-09 4.55E-07 1.77 9.82 19q13.4 49 202487_s_at H2AV -2.25 6.02E-11 3.62E-08 -1.64 -9.66 7p13 50 204661_at CDW52 22.88 1.06E-07 1.35E-05 2.16 9.63 1p36
2.12 inv(3) versus t(8;21)
# affy id HUGO name fc p q stn t Map Location 1 203949. .at MPO -5.73 1.58E-13 3.73E-09 -2.14 -12.41 17q23.1 2 211084. _x_ at PRKCN 6.08 3.25E-10 1.92E-06 1.92 10.59 2p21 3 225010. .at D10S170 2.96 1.16E-11 1.38E-07 1.78 10.37 10q21 4 233955. _x_ at HSPC195 5.19 3.37E-08 8.86E-05 2.18 10.19 5q31.3 5 203948. _s_ at MPO -6.82 1.36E-10 1.07E-06 -1.74 -9.93 17q23.1 6 217963. _s_ at NGFRAP1 29.01 4.74E-07 3.74E-04 2.04 8.67 Xq22.1 7 224516. _s_ at HSPC195 5.87 5.57E-07 3.79E-04 1.92 8.45 5q31.3 8 219478. .at WFDC1 -12.35 6.15E-08 1.28E-04 -1.68 -8.45 16q24.3 9 217226. _s_ at BA108L7.2 3.53 7.38E-08 1.28E-04 1.58 8.38 10q24.31 10 231180. .at -2.35 2.92E-09 1.38E-05 -1.42 -8.23 11 201281. .at ADRM1 -2.17 1.21 E-08 4.62E-05 -1.45 -8.15 20q13.33 12 212423. _at FLJ90798 4.18 7.41 E-08 1.28E-04 1.49 8.07 10q22.3 13 222996. _s_ at HSPC195 4.31 1.08E-06 4.79E-04 1.79 7.98 5q31.3 14 228827. _at -95.46 2.85E-07 2.93E-04 -1.78 -7.91 15 230259. _at -1.91 2.21 E-08 6.52E-05 -1.37 -7.77 16 213716. _s_ at SECTM1 5.01 2.54E-07 2.86E-04 1.44 7.68 17q25 17 211709. _s_ at SCGF -3.55 1.37E-08 4.62E-05 -1.30 -7.56 19q13.3 18 202759. _s_ at AKAP2 -4.91 2.29E-07 2.71 E-04 -1.45 -7.56 9q31-q33 19 219165. .at PDLIM2 3.79 6.33E-07 4.00E-04 1.48 7.55 8p21.2 20 206478. .at KIAA0125 23.32 2.67E-06 8.31 E-04 1.89 7.54 14q32.33 21 205529. _s_ a CBFA2T1 -13.48 6.51 E-07 4.00E-04 -1.63 -7.44 8q22 22 212895. _s_ at ABR 3.03 3.97E-07 3.50E-04 1.38 7.38 17p13.3 23 223534. _s_ at RPS6KL1 -2.20 8.42E-08 1.33E-04 -1.31 -7.37 14q24.2 24 212953. _x_ at CALR -2.47 3.99E-07 3.50E-04 -1.42 -7.33 19p13.3- p13.2 25 206295. .at IL18 3.69 1.85E-06 6.95E-04 1.52 7.33 11q22.2- q22.3 26 202006. .at PTPN12 2.76 6.85E-07 4.00E-04 1.39 7.29 7q11.23 27 220974. _x_ at BA108L7.2 4.34 5.65E-07 3.79E-04 1.37 7.27 10q24.31 28 201243. _s_ at ATP1B1 5.21 2.00E-06 7.03E-04 1.50 7.27 1q22-q25 29 201938. .at CDK2AP1 2.10 7.57E-08 1.28E-04 1.27 7.26 12q24.31 30 207839. _s_ at LOC51754 3.16 2.14E-07 2.66E-04 1.30 7.24 9p13.1 31 203820. _s_ at K0C1 3.93 2.73E-06 8.37E-04 1.53 7.19 7p11 32 202887. _s_ at RTP801 4.32 1.72E-06 6.79E-04 1.44 7.17 10pter- q26.12 33 215051. _x_ at AIF1 2.69 1.90E-07 2.49E-04 1.28 7.17 6p21.3 34 214042 s at RPL22 1.48 7.74E-07 4.16E-04 1.35 7.15 1p36.3- p36.2 57 Ta e + 35 227620_at 3.79 3.71 E-07 3.50E-04 1.27 7.03 36 210150_s_at LAMA5 -4.17 5.29E-07 3.79E-04 -1.31 -7.01 20q13.2- q13.3 37 230659_at KIAA0212 -2.09 5.37E-07 3.79E-04 -1.30 -6.99 3p26.1 38 221773_at 3.81 8.38E-07 4.31 E-04 1.30 6.99 39 226865_at 8.49 5.84E-06 1.21 E-03 1.64 6.98 40 242621_at FLJ32468 -1.58 2.69E-07 2.90E-04 -1.24 -6.95 7q22.1 41 229406_at -11.72 1.19E-06 4.98E-04 -1.39 -6.94 42 214317_x_at RPS9 2.15 7.51 E-08 1.28E-04 1.19 6.93 19q13.4 43 213908_at 3.96 2.61 E-06 8.24E-04 1.38 6.92 44 204494_s_at DKFZP434H132 4.90 6.20E-06 1.21 E-03 1.56 6.89 15q22.33 45 214807_at 2.91 2.89E-06 8.66E-04 1.34 6.80 46 220377_at C14orf110 239.90 8.80E-06 1.40E-03 1.75 6.79 14q32.33 47 221458_at HTR1 F 2.55 2.14E-06 7.23E-04 1.30 6.77 3p12 48 227279_at MGC15737 3.22 4.36E-06 1.08E-03 1.38 6.76 Xq22.1 49 206871_at ELA2 -5.10 6.92E-07 4.00E-04 -1.22 -6.69 19p13.3 50 235199 at 2.76 1.11 E-06 4.79E-04 1.22 6.68
2.13 normal versus t(15;17)
# affy id HUGO name fc stn t Map Location 1 213147_at HOXA10 17.20 7.61 E-48 1.35E-43 1.80 21.98 7p15-p14 2 214651_s_at HOXA9 165.25 6.03E-45 5.33E-41 1.86 21.567p15-p14 3 209732_at CLECSF2 20.01 1.05E-43 6.19E-40 1.69 20.4312p13- p12 4 217848_s_at PP 4.53 1.30E-33 1.43E-30 1.63 19.1010q11.1- q24 5 204425_at ARHGAP4 16.00 7.32E-40 3.24E-36 1.51 18.45 Xq28 6 203948_s_at MPO -4.31 4.91 E-18 4.88E-16 -1.99 -18.4417q23.1 7 235753_at 11.39 2.85E-38 8.41 E-35 1.52 18.22 8 213587_s_at LOC 155066 5.69 1.56E-39 5.53E-36 1.47 18.147q36.1 9 205453_at HOXB2 17.64 8.27E-37 1.83E-33 1.45 17.5217q21- q22 10 213150_at HOXA10 32.28 6.55E-36 1.16E-32 1.44 17.257p15-p14 11 205771_s_at AKAP7 11.23 4.80E-37 1.21 E-33 1.39 17.156q23 12 204563_at SELL 6.36 1.44E-35 2.13E-32 1.39 17.031q23-q25 13 209905_at HOXA9 427.11 6.92E-35 9.41 E-32 1.48 16.977p15-p14 14 211990_at HLA-DPA1 8.89 1.52E-36 2.99E-33 1.37 16.906p21.3 15 206847_s_at HOXA7 7.10 8.12E-36 1.31 E-32 1.37 16.80 7p15-p14 16 212953_x_at CALR -3.76 2.76E-13 1.05E-11 -2.63 -16.73 19p13.3- p13.2 17 201923_at PRDX4 5.34 1.07E-29 8.98E-27 1.41 16.60 Xp22.13 18 203949_at MPO -2.75 3.27E-21 5.78E-19 -1.51 -16.17 17q23.1 19 213844_at HOXA5 26.04 1.50E-33 1.56E-30 1.34 16.137p15-p14 20 241742_at PRAM-1 6.31 4.59E-34 5.80E-31 1.30 15.9919p13.2 21 204362_at SCAP2 14.27 5.48E-34 6.46E-31 1.30 15.957p21-p15 22 221004_s_at ITM2C -6.45 8.06E-14 3.48E-12 -2.07 -15.902q37 23 228113_at STAT3 4.35 9.90E-29 7.00E-26 1.33 15.7917q21 24 236322 at 6.34 1.24E-29 9.99E-27 1.32 15.79 58 Table1+2 25 214797_s_at PCTK3 4.80 5.08E-26 2.15E-23 1.33 15.44 1q31-q32 26 225639_at SCAP2 11.62 1.80E-32 1.77E-29 1.25 15.40 7p21-p15 27 200654_at P4HB -2.36 1.03E-15 6.62E-14 -1.67 -15.39 17q25 28 214450_at CTSW -6.52 9.60E-13 3.22E-11 -2.30 -15.35 11q13.1 29 38487_at STAB1 -7.03 1.98E-12 6.20E-11 -2.21 -14.76 3p21.31 30 235521_at HOXA3 24.52 1.32E-29 1.02E-26 1.24 14.69 7p15-p14 31 231767_at HOXB4 4.88 1.66E-30 1.54E-27 1.18 14.57 17q21- q22 32 200931_s_at VCL 3.67 3.82E-27 2.01 E-24 1.22 14.54 10q22.1- q23 33 238058_at 4.07 7.32E-30 6.47E-27 1.18 14.42 34 205600_x_at HOXB5 2.95 4.70E-28 2.97E-25 1.19 14.39 17q21.3 35 231832_at GALNT4 3.19 6.19E-21 1.01E-18 1.29 14.33 12q21.3- q22 36 236554_x_at EVER2 3.51 5.84E-24 1.75E-21 1.22 14.20 17q25.3 37 216899_s_at SCAP2 6.57 1.91E-29 1.41E-26 1.15 14.17 7p21-p15 38 225314_at MGC45416 2.69 2.33E-26 1.12E-23 1.16 13.93 4p11 39 207375_s_at IL15RA 4.72 1.94E-26 9.54E-24 1.16 13.93 10p15- p14 40 227598_ at LOC 113763 4.28 5.64E-28 3.44E-25 1.13 13.81 7q35 41 204361_s_at SCAP2 9.69 3.06E-28 2.08E-25 1.12 13.77 7p21-p15 42 228904_at 13.76 3.02E-27 1.67E-24 1.16 13.73 43 226106_at ZFP26 4.85 3.68E-28 2.41 E-25 1.11 13.73 11p15.3 44 227353_at EVER2 3.42 1.63E-20 2.44E-18 1.23 13.71 17q25.3 45 222423_at NDFIP1 3.39 2.13E-24 6.97E-22 1.16 13.70 5q31.3 46 213388_at 6.14 2.72E-26 1.27E-23 1.13 13.68 47 227999_at LOC170394 3.01 4.28E-21 7.50E-19 1.20 13.64 10q26.3 48 201753_s_at ADD3 5.82 3.86E-27 2.01 E-24 1.10 13.53 10q24.2- q24.3 49 201719_s_at EPB41 L2 10.16 1.49E-27 8.49E-25 1.10 13.52 6q23 50 210145_at PLA2G4A 6.98 1.16E-27 6.86E-25 1.10 13.50 1q25
2.14 normal versus t(8;21)
# affy id HUGO name fc p q stn t Map Location 1 214651_s_at HOXA9 114455..442266..4400EE--4455 11..7766EE--4400 11..8855 21.54 7p15-p14 2 213147_at HOXA10 1111..117722..5555EE--444433..5500EE--4400 11..6644 20.18 7p15-p14 3 235753_at 1100..227766..9999EE--338866..3399EE--3344 11..4488 17.88 4 205453_at HOXB2 2200..336633..8899EE--337722..1144EE--3333 11..4477 17.66 17q21- q22 5 213150_at HOXA10 39.50 3.93E-36 1.80E-32 1.46 17.37 7p15-p14 6 206847_s_at HOXA7 6.33 3.12E-37 2.14E-33 1.40 17.21 7p15-p14 7 209905_at HOXA9 373.92 7.12E-35 2.79E-31 1.47 16.97 7p15-p14 8 221581_s_at WBSCR5 6.07 3.59E-33 1.23E-29 1.27 15.64 7q11.23 9 213844_at HOXA5 14.53 3.73E-32 1.14E-28 1.26 15.37 7p15-p14 10 235521_at HOXA3 19.62 3.18E-29 7.94E-26 1.23 14.53 7p15-p14 11 217963_s_at NGFRAP1 16.68 2.36E-29 6.47E-26 1.17 14.24 Xq22.1 12 243806_at 4.41 5.47E-27 1.07E-23 1.12 13.65 13 228904 at 13.05 4.26E-27 8.99E-24 1.15 13.65 59 ab e +2 14 225615_at LOC126917 6.55 1.29E-27 2.95E-24 1.10 13.52 1p36.13 15 233955_x_at HSPC195 3.26 3.10E-26 5.32E-23 1.11 13.42 5q31.3 16 227279_at MGC15737 2.67 1.87E-20 1.20E-17 1.19 13.37 Xq22.1 17 213908_at 5.06 1.20E-26 2.19E-23 1.08 13.21 18 205366_s_at H0XB6 33.49 6.39E-26 9.74E-23 1.13 13.21 17q21.3 19 215087_at 3.73 3.61 E-26 5.82E-23 1.05 12.95 20 231767_at H0XB4 3.96 2.89E-25 3.96E-22 1.06 12.93 17q21- q22 21 241370_at 3.39 1.53E-25 2.21 E-22 1.05 12.88 22 236892_s_at 20.18 1.96E-24 2.44E-21 1.06 12.59 23 228365_at L0C144402 8.45 8.27E-25 1.08E-21 1.03 12.58 12q11 24 203017_s_at SSX2IP 3.94 6.95E-24 7.62E-21 1.03 12.52 25 204069_at MEIS1 13.42 4.38E-24 5.01 E-21 1.04 12.43 2p14-p13 26 205601_s_at H0XB5 3.11 2.82E-24 3.36E-21 1.01 12.36 17q21.3 27 239791_at 12.91 1.21 E-23 1.28E-20 1.02 12.23 28 206310_at SPINK2 53.74 2.36E-23 2.23E-20 1.04 12.19 4q12 29 238077_at MGC27385 3.78 1.86E-23 1.82E-20 0.99 12.12 3p21.1 30 208091_s_at DKFZP564K0822 5.35 7.06E-23 5.70E-20 1.00 12.10 7p14.1 31 226206_at FLJ32205 2.54 1.36E-19 7.91 E-17 1.04 12.05 7p22.3 32 230894_s_at 7.46 1.35E-23 1.37E-20 0.98 12.03 33 205600_x_at H0XB5 2.56 8.19E-20 4.88E-17 1.04 12.02 17q21.3 34 226865_at 6.47 3.94E-23 3.49E-20 0.98 11.92 35 222996_s_at HSPC195 2.52 5.88E-23 4.89E-20 0.98 11.92 5q31.3 36 238756_at 4.33 4.37E-23 3.75E-20 0.97 11.90 37 203680_at PRKAR2B 6.19 3.16E-23 2.89E-20 0.97 11.86 7q22- q31.1 38 241706_at LOC 144402 5.37 2.55E-22 1.95E-19 0.96 11.74 12q11 39 204494_s_at DKFZP434H132 2.88 4.33E-22 3.05E-19 0.95 11.60 15q22.33 40 224516_s_at HSPC195 3.18 1.86E-22 1.46E-19 0.94 11.59 5q31.3 41 233467_s_at PHEMX 2.18 4.65E-14 9.67E-12 1.14 11.58 11p15.5 42 204495_s_at DKFZP434H132 2.75 4.31 E-22 3.05E-19 0.95 11.58 15q22.33 43 238778_at FLJ32798 9.22 4.01 E-22 2.97E-19 0.94 11.48 10p11.1 44 227853_at 3.12 1.50E-17 6.34E-15 1.01 11.47 45 202006_at PTPN12 2.49 6.57E-17 2.50E-14 1.00 11.26 7q11.23 46 226134_s_at 5.05 1.67E-21 1.15E-18 0.91 11.20 47 218772_x_at FLJ 10493 2.92 5.63E-17 2.18E-14 0.98 11.09 9q31.2 48 238012_at 2.14 1.19E-16 4.14E-14 0.98 11.04 49 238455_at 4.27 4.48E-21 3.00E-18 0.90 11.04 50 224764 at ARHGAP10 4.58 1.17E-20 7.64E-18 0.90 11.01 10
2.15 t(15;17) versus t(8;21)
# affy id HUGO name fc stn t Map Location 1 214450_at CTSW 28.73 1.65E-13 4.59E-09 3.58 17.73 11q13.1 2 38487_at STAB1 19.69 4.77E-13 4.59E-09 3.26 16.49 3p21.31 3 209732_at CLECSF2 -30.76 2.95E-12 1.46E-08 -3.39 -16.10 12p13- p12 4 211990 at HLA-DPA1 -10.92 1.76E-11 5.09E-08 -2.53 -13.40 6p21.3 5 224839_s_at GPT2 12.98 6.62E-11 1.19E-07 2.37 12.32 16q12.1 6 212509_s_at 10.31 9.35E-11 1.59E-07 2.37 12.20 7 204150_at STAB1 21.33 3.55E-10 4.10E-07 2.36 11.58 3p21.31 8 201596_x_at KRT18 20.06 3.29E-10 3.96E-07 2.28 11.50 12q13 9 221004_s_at ITM2C 3.37 4.65E-13 4.59E-09 1.86 11.42 2q37
10 205349_at GNA15 3.53 3.47E-11 8.35E-08 2.00 11.42 19p13.3
11 205663_at PCBP3 4.49 9.95E-12 3.59E-08 1.92 11.33 21q22.3
12 226878_at -5.52 8.96E-10 7.61 E-07 -2.06 -10.80
13 212953_x_at CALR 2.41 1.19E-12 8.57E-09 1.74 10.78 19p13.3- p13.2
14 227326_at 5.43 2.89E-10 3.63E-07 1.89 10.58
15 217716_s_at SEC61A1 2.09 3.73E-12 1.54E-08 1.70 10.48 3q21.3
16 228113_at STAT3 -5.12 5.53E-10 5.50E-07 -1.86 -10.38 17q21
17 200986_at SERPING1 9.81 1.47E-09 1.09E-06 1.98 10.34 11 q12- q13.1
18 208689_s_at RPN2 1.79 3.03E-12 1.46E-08 1.63 10.17 20q12- q13.1
19 217478_s_at HLA-DMA -5.35 6.89E-10 6.42E-07 -1.81 -10.15 6p21.3
20 204316_at RGS10 -2.45 1.99E-10 2.67E-07 -1.73 -10.10 10q25
21 209021_x_at KIAA0652 4.43 3.36E-11 8.35E-08 1.61 9.83 11p11.12
22 205614_x_at MST1 7.54 3.75E-09 2.30E-06 1.83 9.69 3p21
23 209619_at CD74 -4.60 1.28E-10 1.95E-07 -1.60 -9.66 5q32
24 200953_s_at CCND2 2.70 4.02E-10 4.30E-07 1.65 9.66 12p13
25 208852_s_at CANX 2.32 6.39E-11 1.19E-07 1.57 9.60 5q35
26 208826_x_at HINT1 1.43 5.89E-11 1.19E-07 1.56 9.58 5q31.2
27 201522_x_at SNRPN -3.65 1.70E-11 5.09E-08 -1.53 -9.54 15q12
28 201136_at PLP2 2.76 2.03E-10 2.67E-07 1.56 9.41 Xp11.23
29 201137_s_at HLA-DPB1 -13.39 1.86E-08 7.79E-06 -1.93 -9.37 6p21.3
30 201425_at ALDH2 5.16 1.10E-09 8.76E-07 1.61 9.35 12q24.2
31 204670_x_at HLA-DRB5 -5.72 8.74E-10 7.61 E-07 -1.58 -9.30 6p21.3
32 201952_at ALCAM 4.64 2.50E-09 1.76E-06 1.65 9.30 3q13.1
33 211991_s_at HLA-DPA1 -17.00 2.54E-08 9.11 E-06 -1.85 -9.13 6p21.3
34 209312_x_at HLA-DRB1 -6.80 5.84E-09 3.18E-06 -1.63 -9.09 6p21.3
35 238022_at 4.06 6.47E-11 1.19E-07 1.46 9.09
36 211474_s_at SERPINB6 -5.69 1.90E-08 7.82E-06 -1.74 -9.06 6p25
37 223321_s_at FGFRL1 3.74 4.94E-09 2.89E-06 1.61 9.02 4p16
38 201894_s_at DCN 2.05 1.13E-10 1.81 E-07 1.42 8.86 12q13.2
39 208885_at LCP1 2.18 1.50E-10 2.16E-07 1.42 8.85 13q14.3
40 201923_at PRDX4 -5.83 1.40E-08 6.42E-06 -1.61 -8.82 Xp22.13
41 209344_at TPM4 6.87 2.27E-08 8.69E-06 1.69 8.80 19p13.1
42 227353_at EVER2 -3.83 4.90E-09 2.89E-06 -1.52 -8.79 17q25.3
43 202732_at PKIG 2.65 2.70E-09 1.79E-06 1.49 8.74 20q12- q13.1
44 208306_x_at HLA-DRB4 -7.05 1.62E-08 7.08E-06 -1.57 -8.69 6p21.3
45 55093_at CSGIcA-T 1.87 6.61 E-10 6.36E-07 1.41 8.65 7q36.1
46 201360_at CST3 4.20 2.73E-09 1.79E-06 1.45 8.61 20p11.21
47 221799_at CSGIcA-T 2.51 3.90E-10 4.30E-07 1.38 8.59 7q36.1
48 201581_at DJ971N18.2 2.54 2.69E-09 1.79E-06 1.44 8.58 20p12
49 207721_x_at HINT1 1.55 5.39E-10 5.50E-07 1.38 8.52 5q31.2
50 205035_at CTDP1 2.57 1.34E-08 6.42E-06 1.51 8.51 18q23 61 Table 3 and 4
Table 3
3. One-Versus-AII (OVA)
3.1 11q23 versus rest
# affy id HUGO name fc | P < q stn t Map Location 1 202746_at ITM2A 2.85E-24 8.05E-20 -1.40 -14.06 Xq13.3-Xq21.2 12.91 2 202747_s_at ITM2A 3.31 E-23 4.67E-19 -1.33 -13.40 Xq13.3-Xq21.2 12.74 3 200953_s_at CCND2 -4.13 6.99E-23 6.58E-19 -1.21 -12.64 12p13 4 214651_s_at HOXA9 16.91 7.73E-14 7.53E-11 1.76 12.47 7p15-p14 5 200951_s_at CCND2 -4.70 1.60E-20 1.13E-16 -1.12 -11.63 12p13 6 201830_s_at NET1 -3.86 5.10E-20 2.88E-16 -1.10 -11.41 10p15 7 225831_at LOC 148894 -3.63 1.18E-19 5.56E-16 -1.08 -11.20 1p36.11 8 206847_s_at HOXA7 5.87 3.36E-12 1.73E-09 1.49 10.73 7p15-p14 9 213147_at HOXA10 6.79 2.99E-12 1.65E-09 1.41 10.60 7p15-p14 10 235753_at 10.50 1.61 E-11 6.13E-09 1.59 10.33 11 201015_s_at JUP -5.70 3.82E-17 1.20E-13 -1.00 -10.30 17q21 12 225344_at ERAP140 -3.86 7.59E-17 1.95E-13 -1.02 -10.29 6q22.33 13 201829_at NET1 -2.51 1.29E-17 5.22E-14 -0.99 -10.28 10p15 14 200665_s_at SPARC -9.29 1.02E-16 2.40E-13 -1.01 -10.18 5q31.3-q32 15 235818_at -8.40 5.28E-17 1.49E-13 -0.99 -10.15 16 225653_at -1.86 3.48E-17 1.20E-13 -0.97 -10.10 17 214390_s_at BCAT1 -8.46 1.87E-16 4.06E-13 -1.00 -10.07 12pter-q12 18 226517_at BCAT1 -9.42 3.34E-16 6.75E-13 -1.02 -10.07 12pter-q12 19 213737_x_at 2.30 5.27E-13 3.72E-10 1.13 10.03 20 204082_at PBX3 6.73 7.32E-11 2.11 E-08 1.46 9.67 9q33-q34 21 227297_at 4.62E-15 6.87E-12 -0.99 -9.60 12.11 22 206761_at TACTILE 6.00E-15 8.47E-12 -1.01 -9.60 3q13.13 14.31 23 209905_at HOXA9 30.79 1.17E-10 3.18E-08 1.50 9.53 7p15-p14 24 206009_at ITGA9 -2.94 1.25E-15 2.35E-12 -0.91 -9.45 3p21.3 25 231259_s_at CCND2 -2.38 1.75E-15 3.09E-12 -0.91 -9.41 12p13 26 218966_at MY05C -2.46 2.13E-15 3.54E-12 -0.89 -9.28 15q21 27 221581_s_at WBSCR5 3.27 3.80E-11 1.28E-08 1.14 9.23 7q11.23 28 221235_s_at -2.14 3.45E-15 5.41 E-12 -0.88 -9.21 29 216417_x_at HOXB9 2.85 6.70E-11 1.99E-08 1.16 9.15 17q21.3 30 241756_at -3.10 6.30E-15 8.47E-12 -0.87 -9.08 31 218041_x_at SLC38A2 -1.64 3.37E-12 1.73E-09 -0.97 -8.98 12q 32 242051_at -2.87 1.05E-14 1.32E-11 -0.86 -8.98 33 219188_s_at LRP16 -2.96 1.08E-14 1.32E-11 -0.86 -8.98 11q11 34 212667_at SPARC -4.84 1.65E-14 1.95E-11 -0.86 -8.92 5q31.3-q32 35 220104_at ZAP -2.23 4.58E-14 4.98E-11 -0.86 -8.87 7q34 36 221831_at LOC148894 -2.48 1.75E-13 1.54E-10 -0.87 -8.81 1p36.11 37 213908_at 7.26 6.80E-10 1.40E-07 1.30 8.75 38 219686_at HSA250839 -9.62 2.75E-13 2.10E-10 -0.92 -8.75 4p16.2 39 225285 at -7.72 6.68E-14 7.00E-11 -0.85 -8.72 62 Table 3 and 4 40 200952_s_at CCND2 -2.56 4.37E-14 4.94E-11 -0.83 -8.71 12p13 41 224049_at KCNK17 -2.91 6.94E-14 7.00E-11 -0.84 -8.70 6p21.1 42 209679_s_at LOC57228 -2.41 1.91 E-13 1.54E-10 -0.84 -8.61 12q13.12 43 201029_s_at CD99 -1.87 9.29E-12 3.92E-09 -0.91 -8.59 Xp22.32 44 218825_at ZNEU1 -4.68 8.83E-14 8.32E-11 -0.82 -8.57 9q34.3 45 214439_x_at BIN1 -2.63 1.56E-13 1.43E-10 -0.83 -8.55 2q14 46 213150_at HOXA10 11.23 1.27E-09 2.33E-07 1.28 8.51 7p15-p14 47 228058_at LOC124220 -4.30 7.66E-13 5.03E-10 -0.84 -8.50 16p13.3 48 201564_s_at FSCN1 -4.90 1.88E-13 1.54E-10 -0.82 -8.49 7p22 49 200602_at APP -5.79 1.86E-13 1.54E-10 -0.81 -8.42 21q21.3 50 221832_s_at LOC148894 -2.54 3.02E-13 2.24E-10 -0.81 -8.41 1p36.11
3.2 inv(16) versus rest
# affy id HUGO name fc | ? i q stn t Map Location 1 227567_at -4.44 1.09E-23 3.61 E-19 -1.25 -13.05 2 225055_at DKFZp667M2411 -4.65 8.12E-22 1.34E-17 -1.16 -12.13 17q11.2 3 224952_at DKFZP564D166 -3.64 2.43E-19 2.01 E-15 -1.18 -11.90 17q23.3 4 202370_s_at CBFB -2.54 2.73E-20 3.01 E-16 -1.10 -11.45 16q22.1 5 201497_x_at MYH11 24.43 1.67E-10 9.18E-08 2.11 10.82 16p13.13- p13.12 6 213737_x_at -2.57 1.66E-18 1.09E-14 -1.04 -10.78 7 201496_x_at MYH11 6.76 9.51 E-11 5.61 E-08 1.66 10.72 16p13.13- p13.12 8 200675_at CD81 -3.20 9.31 E-18 4.39E-14 -1.04 -10.70 11p15.5 9 225102_at LOC 152009 -4.43 5.82E-18 3.20E-14 -1.00 -10.44 3q21.3 10 200665_s_at SPARC 4.00 1.11E-11 1.00E-08 1.28 10.36 5q31.3-q32 11 223471_at RAB3IP -2.82 1.34E-16 5.54E-13 -0.96 -9.93 12 228497_at FLIPT1 -5.27 5.36E-16 1.97E-12 -0.97 -9.81 1p13.1 13 218414_s_at NUDE1 -1.90 7.84E-16 2.59E-12 -0.91 -9.50 16p13.11 14 229215_at ASCL2 -6.84 1.68E-15 5.05E-12 -0.92 -9.47 11p15.5 15 227224_at FLJ25604 -3.52 6.44E-15 1.77E-11 -0.91 -9.37 1q24.2 16 231310_at 2.60 5.72E-12 5.90E-09 1.01 9.27 17 232636_at DKFZp547M2010 1.33E-14 2.92E-11 -0.95 -9.27 Xq27.3 10.00 18 203973_s_at CEBPD 2.15 4.87E-12 5.36E-09 0.99 9.14 8p11.2-p11.1 19 211031_s_at CYLN2 -7.45 1.95E-14 4.02E-11 -0.91 -9.11 7q11.23 20 218795_at ACP6 -3.17 9.67E-15 2.46E-11 -0.88 -9.11 1q21 21 204197_s_at RUNX3 -3.20 1.25E-14 2.92E-11 -0.87 -9.00 1p36 22 242520_s_at -4.95 4.22E-14 7.75E-11 -0.89 -8.95 23 224724_at SULF2 6.66 2.80E-09 9.06E-07 1.28 8.84 20q12-13.2 24 219379_x_at ZNF358 -3.01 2.63E-14 5.12E-11 -0.85 -8.82 25 205453_at HOXB2 4.14 7.83E-11 4.88E-08 0.97 8.70 17q21-q22 26 213779_at LOC129080 -3.47 9.77E-14 1.54E-10 -0.84 -8.65 22q12.1 27 226352_at -4.36 7.39E-14 1.22E-10 -0.83 -8.64 28 211026_s_at MGLL -2.49 6.63E-14 1.15E-10 -0.83 -8.63 3q21.3 29 205419_at EBI2 2.98 4.74E-10 2.15E-07 1.01 8.52 13q32.2 30 204563_at SELL 2.76 3.19E-10 1.66E-07 0.95 8.38 1q23-q25 I Table 3 an 4 63 31 207075_at CIAS1 2.64 3.84E-10 1.86E-07 0.95 8.33 1q44 32 205944_s_at CLTCL1 -3.84 3.28E-13 4.92E-10 -0.80 -8.32 22q 11.21 33 213915_at NKG7 -2.95 4.13E-13 5.93E-10 -0.79 -8.26 19q13.33 34 219218_at FLJ23058 -4.23 1.08E-12 1.43E-09 -0.79 -8.14 17q25.3 35 227185_at -1.78 8.82E-13 1.21 E-09 -0.78 -8.12 36 212667_at SPARC 3.29 6.11 E-09 1.71 E-06 1.06 8.11 5q31.3-q32 37 238365_s_at -4.76 2.84E-12 3.47E-09 -0.81 -8.08 38 204661_at CDW52 2.62 4.36E-10 2.03E-07 0.88 8.01 1p36 39 212463_at -2.98 1.52E-12 1.93E-09 -0.77 -8.01 40 227120_at LOC116113 -2.02 9.18E-11 5.52E-08 -0.84 -8.01 6p21.1 41 34210_at CDW52 2.79 9.51 E-10 3.70E-07 0.89 7.93 1p36 42 209822_s_at VLDLR -4.04 3.20E-12 3.64E-09 -0.77 -7.92 9p24 43 229168_at DKFZp434K0621 -3.30 7.81 E-12 7.59E-09 -0.80 -7.88 5q35.3 44 204198_s_at RUNX3 -3.99 2.96E-12 3.49E-09 -0.75 -7.88 1p36 45 229309_at 5.41 2.19E-08 4.36E-06 1.08 7.82 46 206788_s_at CBFB -1.73 2.75E-11 2.16E-08 -0.78 -7.80 16q22.1 47 201432_at CAT -1.76 3.16E-11 2.38E-08 -0.78 -7.78 11p13 48 227856_at FLJ39370 -3.93 5.07E-12 5.41 E-09 -0.74 -7.774q25 49 227533_at -2.24 1.12E-11 1.00E-08 -0.75 -7.72 50 200985_s_at CD59 -4.36 6.74E-12 6.74E-09 -0.74 -7.72 11p13
3.3 inv(3) versus rest
# affy id HUGO name fc P q stn t Map Location 1 205382_s_at DF -6.90 1.05E-23 2.35E-19 -1.25 -13.02 19p13.3 2 223534_s_at RPS6KL1 -2.10 1.42E-14 2.64E-11 -1.13 -10.83 14q24.2 3 202759_s_at AKAP2 -3.56 4.97E-17 3.22E-13 -1.03 -10.53 9q31-q33 4 210115_at RPL39L -8.93 5.75E-17 3.22E-13 -1.00 -10.18 3q27 5 228161_at RAB32 -2.26 3.85E-17 3.22E-13 -0.97 -10.10 6q24.2 6 211709_s_at SCGF -3.88 3.26E-11 1.46E-08 -1.13 -9.97 19q13.3 7 212318_at TRN-SR -2.36 1.92E-14 2.87E-11 -1.01 -9.96 7q32.2 8 223703_at CDA017 -2.86 6.39E-16 2.04E-12 -0.97 -9.93 10q23.1 9 242621_at FLJ32468 -1.54 1.59E-14 2.64E-11 -1.00 -9.92 7q22.1 10 205131_x_at SCGF -7.32 8.67E-17 3.88E-13 -0.95 -9.90 19q13.3 11 212953_x_at CALR -2.91 1.77E-16 6.62E-13 -0.95 -9.83 19p13.3-p13.2 12 200700_s_at KDELR2 -2.52 3.93E-15 8.80E-12 -0.96 -9.77 7p22.2 13 203949_at MPO -4.18 1.78E-13 1.99E-10 -0.99 -9.70 17q23.1 14 214575_s_at AZU1 -6.66 8.62E-16 2.21 E-12 -0.92 -9.57 19p13.3 15 231300_at LOC90835 -3.10 1.11E-14 2.25E-11 -0.93 -9.45 16p11.2 16 210783_x_at SCGF -6.82 8.90E-16 2.21 E-12 -0.91 -9.45 19q13.3 17 203948_s_at MPO -5.17 1.92E-13 2.04E-10 -0.92 -9.19 17q23.1 18 205248_at C21orf5 -1.92 4.97E-13 4.84E-10 -0.91 -9.03 21q22.2 19 202185_at PLOD3 -2.00 2.36E-12 1.89E-09 -0.93 -9.02 7q22 20 200654_at P4HB -2.40 5.53E-11 2.29E-08 -0.98 -9.00 17q25 21 204921_at GAS8 -3.13 1.65E-14 2.64E-11 -0.85 -8.89 16q24.3 22 202760_s_at AKAP2 -4.47 1.34E-13 1.57E-10 -0.87 -8.85 9q31-q33 23 224841 x at 1.53 3.84E-09 5.81 E-07 1.07 8.83 I 64 Table 3 and 4 24 204647_at HOMER3 -4.41 3.11 E-14 4.36E-11 -0.84 -8.80 19p13.11 25 224886_at STUB1 -1.81 2.17E-12 1.80E-09 -0.89 -8.79 16p13.3 26 230044_at -2.96 7.03E-12 4.63E-09 -0.91 -8.79 27 230259_at -1.66 7.17E-11 2.68E-08 -0.95 -8.78 28 231736_x_at MGST1 -3.78 6.77E-12 4.59E-09 -0.90 -8.77 12p12.3-p12.1 29 201186_at LRPAP1 -2.55 6.42E-13 5.75E-10 -0.86 -8.65 4p16.3 30 204301_at KIAA0711 -9.40 9.84E-14 1.30E-10 -0.84 -8.65 8p23.2 31 208689_s_at RPN2 -2.01 3.95E-10 9.52E-08 -0.95 -8.60 20q12-q13.1 32 214315_x_at CALR -2.04 1.12E-11 6.57E-09 -0.88 -8.57 19p13.3-p13.2 33 204548_at STAR -9.71 1.32E-13 1.57E-10 -0.83 -8.57 8p11.2 34 224741_x_at 1.52 5.30E-09 7.37E-07 1.02 8.56 35 221739_at IL27w -1.81 5.71 E-10 1.25E-07 -0.95 -8.52 19p13.3 36 211048_s_at ERP70 -2.54 2.04E-13 2.08E-10 -0.82 -8.51 7q35 37 233955_x_at HSPC195 3.20 1.69E-07 1.17E-05 1.26 8.43 5q31.3 38 225010_at D10S170 1.85 3.33E-09 5.22E-07 0.97 8.37 10q21 39 239656_at -2.19 3.51 E-12 2.45E-09 -0.83 -8.37 40 208308_s_at GPI -2.28 1.00E-09 2.08E-07 -0.92 -8.32 19q13.1 41 227432_s_at INSR -2.55 9.60E-11 3.36E-08 -0.87 -8.27 19p13.3-p13.2 42 224918_x_at MGST1 -3.43 2.52E-10 6.97E-08 -0.88 -8.27 12p12.3-p12.1 43 202487_s_at H2AV -1.91 9.08E-09 1.09E-06 -0.98 -8.25 7p13 44 217225_x_at LOC283820 -1.79 1.49E-10 4.97E-08 -0.87 -8.24 16p13.13 45 226789_at -2.33 1.17E-11 6.70E-09 -0.82 -8.21 46 230480_at HIWI2 -3.24 6.07E-13 5.67E-10 -0.79 -8.20 11q21 47 209836_x_at MGC5178 -1.81 2.73E-10 7.37E-08 -0.87 -8.20 16p12.1 48 201004_at SSR4 -1.81 1.56E-11 8.12E-09 -0.82 -8.16 Xq28 49 240672_at -1.54 2.12E-12 1.80E-09 -0.79 -8.14 50 240443 at -1.74 1.55E-11 8.12E-09 -0.81 -8.12
3.4 t( 15; 17) versus rest
# affy id HUGO name fc P q stn t Map Location 1 211990_at HLA-DPA1 6.59E-39 1.59E-34 -1.98 -20.66 6p21.3 10.73 2 211474_s_at SERPINB6 -4.87 1.86E-30 2.25E-26 -1.55 -16.18 6p25 3 209732_at CLECSF2 4.68E-28 3.77E-24 -1.64 -16.06 12p13-p12 33.59 4 214450_at CTSW 8.57 4.43E-13 4.79E-11 2.57 16.03 11q13.1 5 38487_at STAB1 10.15 1.20E-12 1.18E-10 2.68 15.65 3p21.31 6 204425_at ARHGAP4 1.39E-27 8.41 E-24 -1.53 -15.46 Xq28 17.49 7 221004_s_at ITM2C 5.41 2.38E-13 2.73E-11 2.24 15.44 2q37 8 212953_x_at CALR 3.12 1.47E-13 1.77E-11 2.01 14.81 19p13.3-p13.2 9 209619_at CD74 -4.79 5.24E-21 4.87E-18 -1.50 -14.59 5q32 10 201923_at PRDX4 -6.70 4.87E-27 2.35E-23 -1.39 -14.52 Xp22.13 11 208306_x_at HLA-DRB4 -7.49 1.29E-26 5.17E-23 -1.38 -14.39 6p21.3 12 205771_s_at AKAP7 -8.84 2.49E-26 8.59E-23 -1.38 -14.32 6q23 13 209312_x_at HLA-DRB1 -7.02 3.98E-26 1.20E-22 -1.37 -14.24 6p21.3 14 201137_s_at HLA-DPB1 - 4.78E-25 1.15E-21 -1.39 -14.10 6p21.3 65 Table 3 and 4 15 217478_s_at HLA-DMA -5.66 3.09E-25 8.29E-22 -1.31 -13.68 6p21.3 16 200931_s_at VCL -3.69 4.10E-24 9.01 E-21 -1.30 -13.44 10q22.1-q23 17 204670_x_at HLA-DRB5 -5.67 6.80E-22 9.11 E-19 -1.31 -13.25 6p21.3 18 227353_at EVER2 -3.66 7.95E-22 1.01 E-18 -1.31 -13.24 17q25.3 19 204661_at CDW52 6.93E-23 1.29E-19 -1.29 -13.05 1p36 21.19 20 238022_at 6.26 9.58E-12 7.65E-10 1.92 13.00 21 209288_s_at CDC42EP3 -7.86 1.01 E-23 2.04E-20 -1.24 -12.99 2p21 22 200654_at P4HB 2.04 4.76E-15 8.84E-13 1.46 12.88 17q25 23 217848_s_at PP -3.29 1.17E-20 9.72E-18 -1.26 -12.71 10q11.1-q24 24 211991_s_at HLA-DPA1 5.77E-22 8.67E-19 -1.25 -12.64 6p21.3 17.79 25 201719_s_at EPB41 L2 6.10E-22 8.67E-19 -1.23 -12.54 6q23 11.63 26 208982_at PECAM1 -4.98 1.27E-22 2.19E-19 -1.20 -12.53 17q23 27 203948_s_at MPO 2.62 1.47E-17 5.58E-15 1.29 12.43 17q23.1 28 34210_at CDW52 1.88E-21 2.16E-18 -1.23 -12.41 1p36 26.61 29 236554_x_at EVER2 -3.45 3.58E-21 3.76E-18 -1.20 -12.37 17q25.3 30 203535_at S100A9 -7.50 4.64E-22 7.47E-19 -1.18 -12.29 1q21 31 213587_s_at LOC155066 -5.24 2.40E-21 2.63E-18 -1.20 -12.23 7q36.1 32 205624_at CPA3 6.80 7.28E-12 6.00E-10 1.63 12.18 3q21-q25 33 221059_s_at CHST6 -4.81 8.71 E-22 1.05E-18 -1.16 -12.14 16q22 34 228113_at STAT3 -3.88 3.84E-21 3.78E-18 -1.17 -12.08 17q21 35 224918_x_at MGST1 2.47 4.93E-14 7.00E-12 1.38 12.07 12p12.3-p12.1 36 217716_s_at SEC61A1 2.09 9.63E-12 7.65E-10 1.62 12.04 3q21.3 37 221865_at DKFZp547P234 -3.10 1.39E-20 1.12E-17 -1.15 -11.91 9q33.1 38 227598_at LOC113763 -3.86 3.91 E-21 3.78E-18 -1.13 -11.83 7q35 39 201522_x_at SNRPN -3.86 3.58E-15 7.09E-13 -1.28 -11.80 15q12 40 204362_at SCAP2 7.84E-21 7.01 E-18 -1.14 -11.80 7p21-p15 10.33 41 205663_at PCBP3 4.02 9.90E-11 6.03E-09 1.81 11.76 21q22.3 42 231736_x_at MGST1 2.65 8.34E-13 8.43E-11 1.39 11.67 12p12.3-p12.1 43 225639_at SCAP2 -9.34 1.14E-20 9.72E-18 -1.11 -11.62 7p21-p15 44 215193_x_at HLA-DRB1 -6.71 4.49E-20 3.39E-17 -1.12 -11.60 6p21.3 45 204046_at PLCB2 -5.34 4.94E-20 3.52E-17 -1.12 -11.58 15q15 46 232617_at CTSS -5.56 5.25E-20 3.62E-17 -1.13 -11.58 1q21 47 223280_x_at MS4A6A 1.88E-19 1.20E-16 -1.16 -11.53 11q12.1 17.22 48 203299_s_at AP1S2 -4.00 2.23E-20 1.73E-17 -1.10 -11.49 Xp22.31 49 230264_s_at AP1S2 -5.59 4.96E-20 3.52E-17 -1.11 -11.46 Xp22.31 50 241742_at PRAM-1 -7.38 1.34E-19 8.72E-17 -1.11 -11.39 19p13.2
3.5 t(8;21) versus rest
# affy id HUGO name fc p q stn t Map Location 1 225615_at LOC126917 -6.21 2.45E-21 4.69E-17 -1.14 -11.93 1p36.13 2 224764_at ARHGAP10 -6.00 3.05E-21 4.69E-17 -1.14 -11.91 10 3 201944_at HEXB -2.53 3.42E-19 3.50E-15 -1.05 -10.97 5q13 4 200788 s at PEA15 -2.30 9.17E-17 2.17E-13 -1.07 -10.77 1q21.1 66 Table 3 and 4 5 204494_s_at DKFZP434H132 -3.15 1.00E-18 7.67E-15 -1.03 -10.76 15q22.33 6 215087_at -3.23 1.50E-18 9.23E-15 -1.03 -10.72 7 209500_x_at TNFSF13 -3.17 2.95E-18 1.47E-14 -1.03 -10.66 17p13.1 8 221581_s_at WBSCR5 -5.63 3.36E-18 1.47E-14 -1.03 -10.63 7q11.23 9 208890_s_at PLXNB2 -3.57 6.32E-18 2.16E-14 -1.02 -10.60 22q13.33
10 210314_x_at TNFSF13 -3.73 1.52E-17 4.25E-14 -1.02 -10.53 17p13.1
11 238077_at MGC27385 -3.41 5.29E-18 2.03E-14 -1.00 -10.47 3p21.1
12 201425_at ALDH2 -7.89 1.20E-17 3.67E-14 -1.01 -10.43 12q24.2
13 220974_x_at BA108L7.2 -4.27 7.46E-17 1.91 E-13 -1.02 -10.41 10q24.31
14 227279_at MGC15737 -2.41 1.39E-15 1.94E-12 -0.96 -9.83 Xq22.1
15 204495_s_at DKFZP434H132 -3.01 1.81 E-16 3.97E-13 -0.94 -9.79 15q22.33
16 201105_at LGALS1 -4.58 3.24E-16 6.63E-13 -0.94 -9.75 22q13.1
17 205639_at AOAH -4.24 9.54E-16 1.63E-12 -0.95 -9.75 7p14-p12
18 201360_at CST3 -3.74 1.17E-15 1.83E-12 -0.95 -9.73 20p11.21
19 226865_at -5.11 5.19E-16 9.95E-13 -0.95 -9.71
20 220066_at CARD15 -6.40 5.68E-16 1.03E-12 -0.91 -9.54 16p12-q21
21 200838_at CTSB -2.84 1.19E-15 1.83E-12 -0.92 -9.50 8p22
22 206120_at CD33 -4.35 1.32E-15 1.92E-12 -0.90 -9.39 19q13.3
23 227276_at TEM7R -2.75 2.11 E-15 2.70E-12 -0.90 -9.38 10p12.1
24 207075_at CIAS1 -3.91 1.63E-15 2.17E-12 -0.90 -9.38 1q44
25 201850_at CAPG -5.16 3.03E-15 3.72E-12 -0.91 -9.35 2cen-q24
26 201887_at IL13RA1 -3.15 4.60E-15 5.44E-12 -0.88 -9.20 Xq24
27 240572_s_at -3.62 5.33E-15 6.07E-12 -0.87 -9.12
28 201596_x_at KRT18 -9.57 9.31 E-15 1.02E-11 -0.89 -9.11 12q13
29 224393_s_at CECR6 -8.98 1.63E-14 1.73E-11 -0.91 -9.11
30 217226_s_at BA108L7.2 -2.91 3.09E-14 3.06E-11 -0.87 -8.99 10q24.31
31 223398_at MGC11115 -2.54 3.92E-14 3.47E-11 -0.88 -8.99 9q22.2
32 203017_s_at SSX2IP -2.61 3.10E-13 2.06E-10 -0.90 -8.98
33 207839_s_at LOC51754 -2.67 5.30E-11 1.56E-08 -0.99 -8.96 9p 13.1
34 214835_s_at SUCLG2 -3.35 4.18E-14 3.56E-11 -0.87 -8.94 3p14.2
35 212828_at SYNJ2 -2.60 3.42E-14 3.29E-11 -0.86 -8.92 6q25.3
36 212895_s_at ABR -2.69 1.23E-13 8.80E-11 -0.87 -8.87 17p13.3
37 212993_at SAP18 -5.24 2.15E-14 2.20E-11 -0.85 -8.84 13q11
38 223132_s_at TRIM8 -2.39 3.76E-14 3.47E-11 -0.85 -8.82 10q24.3
39 227995_at -6.99 7.53E-14 5.78E-11 -0.89 -8.81
40 225245_x_at H2AFJ -3.51 3.96E-14 3.47E-11 -0.84 -8.78 12p12
41 224049_at KCNK17 -2.80 5.16E-14 4.06E-11 -0.85 -8.74 6p21.1
42 202670_at MAP2K1 -2.34 5.03E-14 4.06E-11 -0.84 -8.74 15q22.1- q22.33
43 211084_x_at PRKCN -3.82 6.03E-12 2.64E-09 -0.90 -8.69 2p21
44 219690_at FLJ22573 -2.40 5.15E-14 4.06E-11 -0.83 -8.68 19q13.11
45 212423_at FLJ90798 -4.03 8.22E-14 6.16E-11 -0.83 -8.65 10q22.3
46 219165_at PDLIM2 -2.76 4.30E-13 2.54E-10 -0.84 -8.59 8p21.2
47 201952_at ALCAM -2.81 4.16E-13 2.50E-10 -0.84 -8.56 3q13.1
48 241370_at -2.43 1.31 E-13 9.14E-11 -0.82 -8.54
49 205419_at EBI2 -4.18 1.20E-13 8.78E-11 -0.81 -8.50 13q32.2
50 204487_s_at KCNQ1 -6.32 3.22E-13 2.06E-10 -0.82 -8.49 11p15.5 Table 3 and 4
Table 4
4. All-Pairs (AP)
4.1 11q23 versus inv(16)
# affy id HUGO name fc | P i q stn t Map Location 1 213737_x_at 3.73 1.13E-15 1.73E-11 2.10 13.96 2 200665_s_at SPARC -16.71 3.03E-13 1.32E-09 -2.29 -13.74 5q31.3-q32 3 200953_s_at CCND2 -4.22 1.13E-15 1.73E-11 -1.89 -13.24 12p13 4 214651_s_at HOXA9 24.48 6.34E-14 4.83E-10 2.09 12.83 7p15-p14 5 202746_at ITM2A -15.51 1.87E-12 5.21 E-09 -2.15 -12.76 Xq13.3- Xq21.2 6 202747_s_at ITM2A -15.29 3.80E-12 7.25E-09 -2.03 -12.22 Xq13.3- Xq21.2 7 231310_at -4.48 1.13E-14 1.15E-10 -1.64 -11.74 8 200951_s_at CCND2 -5.06 4.26E-13 1.63E-09 -1.72 -11.64 12p13 9 202551_s_at CRIM1 -4.41 2.93E-13 1.32E-09 -1.63 -11.30 2p21 10 206847_s_at HOXA7 6.89 1.31 E-12 4.43E-09 1.67 10.96 7p15-p14 11 227567_at 5.37 2.91 E-13 1.32E-09 1.58 10.93 12 201497_x_at MYH11 -25.07 1.61 E-10 1.34E-07 -2.11 -10.83 16p13.13- p13.12 13 205453_at HOXB2 -7.71 7.13E-12 1.28E-08 -1.64 -10.82 17q21-q22 14 235753_at 13.56 9.87E-12 1.51 E-08 1.80 10.62 15 201496_x_at MYH11 -6.90 6.26E-11 7.35E-08 -1.73 -10.60 16p13.13- P13.12 16 212667_at SPARC -8.20 5.65E-11 6.89E-08 -1.65 -10.40 5q31.3-q32 17 224049_at KCNK17 -4.41 9.00E-11 9.46E-08 -1.66 -10.31 6p21.1 18 213147_at HOXA10 6.19 3.53E-12 7.19E-09 1.50 10.20 7p15-p14 19 229215_at ASCL2 10.61 2.45E-11 3.40E-08 1.55 9.93 11p15.5 20 203949_at MPO -3.22 2.23E-12 5.29E-09 -1.38 -9.79 17q23.1 21 209905_at HOXA9 81.21 7.73E-11 8.74E-08 1.69 9.76 7p15-p14 22 226517_at BCAT1 -10.39 6.14E-10 3.82E-07 -1.62 -9.66 12pter-q12 23 202931_x_at BIN1 -2.97 2.31 E-12 5.29E-09 -1.32 -9.58 2q14 24 213908_at 15.53 1.14E-10 1.10E-07 1.59 9.54 25 201830_s_at NET1 -4.02 1.63E-10 1.34E-07 -1.45 -9.52 10p15 26 223471_at RAB3IP 3.55 8.58E-12 1.45E-08 1.35 9.50 27 201029_s_at CD99 -1.93 2.43E-12 5.29E-09 -1.31 -9.48 Xp22.32 28 224952_at DKFZP564D166 3.54 1.88E-12 5.21 E-09 1.27 9.31 17q23.3 29 204082_at PBX3 5.48 1.81E-10 1.45E-07 1.49 9.25 9q33-q34 30 228058_at LOC124220 -5.44 9.13E-12 1.47E-08 -1.27 -9.16 16p13.3 31 225831_at LOC148894 -3.50 2.57E-10 1.96E-07 -1.35 -9.05 1p36.11 32 205330_at MN1 -16.11 4.51 E-09 1.52E-06 -1.71 -9.04 22q12.1 33 202370_s_at CBFB 3.04 1.34E-10 1.20E-07 1.36 9.03 16q22.1 34 225102_at LOC152009 5.50 1.44E-10 1.26E-07 1.34 8.98 3q21.3 35 210139_s_at PMP22 -8.84 3.42E-09 1.26E-06 -1.52 -8.92 17p12-p11.2 36 211012_s_at PML -2.72 4.71 E-11 5.99E-08 -1.22 -8.76 15q22 37 200602_at APP -6.17 1.23E-10 1.14E-07 -1.24 -8.73 21q21.3 68 Table 3 and 4 38 203733_at MYLE 3.27 8.06E-11 8.78E-08 1.24 8.72 16p13.2 39 228496_s_at CRIM1 -2.82 1.15E-10 1.10E-07 -1.23 -8.70 2p21 40 226137_at -3.57 2.49E-09 1.07E-06 -1.38 -8.69 41 214452_at BCAT1 -4.11 1.17E-09 6.73E-07 -1.30 -8.60 12pter-q12 42 203329_at PTPRM -5.80 7.33E-09 2.17E-06 -1.48 -8.60 18p11.2 43 241706_at LOC144402 6.03 4.36E-10 2.96E-07 1.26 8.52 12q11 44 213150_at HOXA10 11.20 1.28E-09 7.06E-07 1.38 8.51 7p15-p14 45 201828_x_at CXX1 2.80 1.75E-11 2.54E-08 1.15 8.51 Xq26 46 202265_at BMI1 3.17 4.25E-10 2.95E-07 1.25 8.48 10p11.23 47 210006_at DKFZP5640243 2.23 5.26E-10 3.42E-07 1.26 8.46 3p21.1 48 225285_at -9.01 3.35E-09 1.26E-06 -1.31 -8.44 49 242738_s_at -2.35 5.69E-10 3.62E-07 -1.22 -8.43 50 218966_at MY05C -2.93 2.74E-09 1.13E-06 -1.28 -8.36 15q21
4.2 11q23 versus inv(3) affy id HUGO name fc | P q stn t Map Location 1 204082_at PBX3 8.05 2.96E-11 4.56E-07 1.56 9.79 9q33-q34 2 226789_at 3.17 7.24E-11 4.56E-07 1.31 8.77 3 225344_at ERAP140 -4.35 2.49E-07 4.83E-05 -1.77 -8.74 6q22.33 4 214651_s_at HOXA9 4.34 4.49E-11 4.56E-07 1.28 8.67 7p15-p14 5 222982_x_at SLC38A2 -1.93 7.96E-10 1.84E-06 -1.31 -8.55 12q 6 213893_x_at PMS2L5 2.34 7.87E-11 4.56E-07 1.26 8.53 7q11-q22 7 236398_s_at 6.39 2.46E-10 1.12E-06 1.29 8.52 8 235753_at 4.79 2.97E-10 1.12E-06 1.27 8.39 9 233955_x_at HSPC195 -4.27 9.34E-09 6.01 E-06 -1.34 -8.38 5q31.3 10 210006_at DKFZP5640243 2.30 3.38E-10 1.12E-06 1.26 8.35 3p21.1 11 235199_at -3.81 2.13E-07 4.41 E-05 -1.54 -8.32 12 203733_at MYLE 2.89 5.18E-10 1.33E-06 1.22 8.12 16p13.2 13 212318_at TRN-SR 2.59 4.46E-10 1.29E-06 1.21 8.10 7q32.2 14 202053_s_at ALDH3A2 2.81 1.73E-09 2.56E-06 1.22 7.94 17p11.2 15 214643_x_at BIN1 -4.34 2.80E-07 5.15E-05 -1.43 -7.94 2q14 16 209905_at HOXA9 6.89 1.61 E-09 2.56E-06 1.21 7.93 7p15-p14 17 228083_at CACNA2D4 8.25 1.77E-09 2.56E-06 1.21 7.91 12p13.33 18 225386_s_at LOC92906 6.11 1.05E-09 2.22E-06 1.17 7.84 2p22.2 19 223703_at CDA017 3.76 3.59E-09 3.24E-06 1.21 7.80 10q23.1 20 200602_at APP -9.73 7.82E-07 1.01 E-04 -1.48 -7.75 21q21.3 21 212782_x_at POLR2J 2.42 3.77E-09 3.24E-06 1.15 7.66 7q11.2 22 208116_s_at MAN1A1 -4.72 9.63E-07 1.16E-04 -1.47 -7.63 6q22 23 208967_s_at AK2 3.86 8.89E-09 5.89E-06 1.21 7.62 1p34 24 215667_x_at PMS2L5 1.93 2.43E-09 3.01 E-06 1.13 7.62 7q11-q22 25 225389_at BTBD6 2.27 1.62E-09 2.56E-06 1.12 7.60 14q32 26 221036_s_at PSFL 2.03 1.74E-09 2.56E-06 1.12 7.57 15q21.3 27 214430_at GLA 2.10 2.07E-09 2.82E-06 1.11 7.51 Xq22 28 206440_at LIN7A 8.97 8.85E-09 5.89E-06 1.16 7.49 12q21 29 230051 at -4.16 5.08E-07 7.64E-05 -1.32 -7.48 69 I able ά an 30 209836_x_at MGC5178 2.05 2.47E-09 3.01 E-06 1.10 7.47 16p12.1 31 202961_s_at ATP5J2 2.24 5.44E-09 4.35E-06 1.11 7.45 7q22.1 32 212174_at AK2 3.70 6.56E-09 4.90E-06 1.13 7.45 1p34 33 213370_s_at SFMBT 1.98 3.04E-09 3.24E-06 1.10 7.44 3p21.31 34 222996_s_at HSPC195 -4.05 7.45E-07 9.81 E-05 -1.34 -7.43 5q31.3 35 202054_s_at ALDH3A2 4.23 2.86E-09 3.24E-06 1.09 7.42 17p11.2 36 224516_s_at HSPC195 -5.00 2.99E-07 5.38E-05 -1.26 -7.41 5q31.3 37 206847_s_at HOXA7 2.83 3.35E-09 3.24E-06 1.10 7.41 7p15-p14 38 201186_at LRPAP1 3.21 7.87E-09 5.70E-06 1.12 7.39 4p16.3 39 219126_at XAP135 1.82 3.30E-09 3.24E-06 1.09 7.38 6q27 40 219991_at SLC2A9 2.18 5.75E-09 4.44E-06 1.11 7.38 4p16-p15.3 41 202605_at GUSB 3.16 4.47E-09 3.70E-06 1.10 7.37 7q21.11 42 213908_at 3.92 1.51 E-08 8.34E-06 1.15 7.37 43 223207_x_at PHP14 1.80 3.42E-09 3.24E-06 1.09 7.36 9q34.3 44 220924_s_at SLC38A2 -1.62 3.76E-09 3.24E-06 -1.08 -7.34 12q 45 200654_at P4HB 2.25 8.68E-09 5.89E-06 1.09 7.28 17q25 46 206478_at KIAA0125 -13.74 3.61 E-06 2.61 E-04 -1.64 -7.27 14q32.33 47 218041_x_at SLC38A2 -1.65 1.58E-08 8.49E-06 -1.09 -7.21 12q 48 214453_s_at IFI44 -4.71 1.66E-06 1.59E-04 -1.34 -7.18 1p31.1 49 231300_at LOC90835 3.98 2.03E-08 9.99E-06 1.11 7.18 16p11.2 50 209696_at FBP1 4.25 3.05E-08 1.29E-05 1.14 7.17 9q22.3
4.3 11q23 versus t(15;17)
# affy id HUGO name fc stn t Map Location 1 221004_s_at ITM2C -11.20 1.59E-14 7.61 E-11 -2.87 -17.09 2q37 2 38487_at STAB1 -16.01 3.30E-13 5.91E-10 -2.90 -16.10 3p21.31 3 203948_s_at MPO -6.05 4.56E-20 1.14E-15 -2.14 -15.28 17q23.1 4 205624_at CPA3 -35.38 6.12E-12 5.68E-09 -3.00 -14.74 3q21-q25 5 212953_x_at CALR -3.21 1.82E-14 7.61 E-11 -2.20 -14.27 19p13.3- p13.2 6 214450_at CTSW -6.21 4.49E-14 1.36E-10 -2.19 -14.03 11q13.1 7 200953_s_at CCND2 -6.31 2.30E-12 2.80E-09 -2.26 -13.45 12p13 8 214651_s_at HOXA9 234.13 3.24E-14 1.16E-10 2.39 13.42 7p15-p14 9 203949_at MPO -4.22 1.85E-17 2.31 E-13 -1.87 -13.25 17q23.1 10 238022_at -6.27 2.35E-12 2.80E-09 -1.99 -12.44 11 206871 _at ELA2 -4.10 1.64E-16 1.37E-12 -1.75 -12.43 19p13.3 12 233072_at KIAA1857 -12.50 6.74E-11 3.12E-08 -2.26 -12.31 9q34 13 213147_at HOXA10 23.75 2.86E-13 5.88E-10 2.04 12.19 7p15-p14 14 201029_s_at CD99 -2.27 1.40E-15 8.79E-12 -1.62 -11.54 Xp22.32 15 204150_at STAB1 -19.83 3.61 E-10 1.14E-07 -2.25 -11.52 3p21.31 16 206847_s_at HOXA7 9.16 4.76E-13 7.95E-10 1.78 11.45 7p15-p14 17 210788_s_at retSDR4 -2.58 1.11 E-11 8.39E-09 -1.79 -11.35 14q22.3 18 209448_at HTATIP2 10.11 1.01 E-12 1.58E-09 1.80 11.31 11p15.1 19 200951_s_at CCND2 -7.13 1.97E-10 7.68E-08 -1.93 -11.10 12p13 20 205663_at PCBP3 -3.88 3.71 E-11 1.90E-08 -1.79 -11.09 21 q22.3 21 212509 s at -6.33 1.39E-10 6.21 E-08 -1.87 -11.03 70 I able ά and 4 22 206761_at TACTILE -25.65 1.23E-09 2.84E-07 -2.20 -10.83 3q13.13 23 235753_at 16.24 7.41 E-12 6.19E-09 1.86 10.77 24 231736_x_at MGST1 -2.95 1.27E-13 2.89E-10 -1.53 -10.74 12p12.3- p12.1 25 213587_s_at LOC155066 7.68 8.23E-12 6.65E-09 1.74 10.58 7q36.1 26 224918_x_at MGST1 -2.77 4.90E-14 1.36E-10 -1.49 -10.57 12p12.3- p12.1 27 201596_x_at KRT18 -9.08 5.27E-10 1.50E-07 -1.81 -10.49 12q13 28 205349_at GNA15 -3.93 1.96E-12 2.73E-09 -1.53 -10.47 19p13.3 29 217848_s_at PP 3.79 3.05E-13 5.88E-10 1.50 10.44 10q11.1-q24 30 201522_x_at SNRPN 4.60 7.40E-14 1.85E-10 1.46 10.39 15q12 31 205771 _s_at AKAP7 9.76 6.69E-12 5.78E-09 1.62 10.38 6q23 32 200952_s_at CCND2 -3.93 2.46E-10 8.91 E-08 -1.67 -10.25 12p13 33 225532_at LOC91768 -5.23 7.13E-10 1.88E-07 -1.73 -10.17 18q11.1 34 225386_s_at LOC92906 35.64 2.81 E-11 1.67E-08 1.73 10.16 2p22.2 35 221253_s_at MGC3178 -3.09 1.65E-10 7.12E-08 -1.61 -10.14 6p24.3 36 218404_at SNX10 6.55 1.28E-11 9.41 E-09 1.55 10.03 7p15.2 37 204425_at ARHGAP4 15.70 3.11 E-11 1.80E-08 1.63 9.99 Xq28 38 204082_at PBX3 8.58 2.56E-11 1.66E-08 1.58 9.93 9q33-q34 39 209905_at HOXA9 701.37 6.10E-11 2.94E-08 1.77 9.88 7p15-p14 40 217716_s_at SEC61A1 -1.97 6.02E-12 5.68E-09 -1.43 -9.86 3q21.3 41 213571_s_at EIF4EL3 2.56 1.14E-12 1.67E-09 1.41 9.85 2q37.1 42 225570_at SLC41A1 3.46 2.26E-12 2.80E-09 1.41 9.81 1q32.1 43 223663_at FLJ37970 7.30 4.86E-12 5.07E-09 1.41 9.71 11q12.3 44 241383_at -4.20 3.65E-09 6.44E-07 -1.74 -9.68 45 219837_s_at C17 -67.10 8.83E-09 1.18E-06 -2.02 -9.65 4p16-p15 46 210140_at CST7 -6.71 1.39E-09 3.08E-07 -1.61 -9.65 20p11.21 47 208852_s_at CANX -2.25 6.37E-11 3.01 E-08 -1.43 -9.58 5q35 48 216417_x_at HOXB9 3.56 4.25E-12 4.63E-09 1.38 9.57 17q21.3 49 212813_at JAM3 -4.92 4.22E-09 7.05E-07 -1.69 -9.54 11q25 50 202746_at ITM2A -18.16 8.43E-09 1.14E-06 -1.85 -9.52 Xq13.3- Xq21.2
4.4 11q23 versus t(8;21) affy id HUGO name fc | P q stn t Map Location 1 214651_s_at HOXA9 206.03 3.28E-14 1.03E-09 2.38 13.41 7p15-p14 2 221581_s_at WBSCR5 9.58 9.94E-14 1.56E-09 1.98 12.37 7q11.23 3 213147_at HOXA10 15.43 4.12E-13 3.22E-09 1.91 11.80 7p15-p14 4 206847_s_at HOXA7 8.17 9.28E-13 5.26E-09 1.83 11.41 7p15-p14 5 235753_at 14.64 8.54E-12 2.97E-08 1.82 10.68 6 201105_at LGALS1 6.65 1.61 E-12 7.21 E-09 1.54 10.34 22q13.1 7 227853_at 3.55 1.68E-13 1.76E-09 1.47 10.30 8 209905_at HOXA9 614.03 6.13E-11 1.37E-07 1.77 9.87 7p15-p14 9 203949_at MPO -3.89 1.01 E-12 5.26E-09 -1.40 -9.82 17q23.1 10 210314_x_at TNFSF13 4.55 4.40E-12 1.72E-08 1.42 9.72 17p13.1 11 213908_at 15.54 1.15E-10 2.13E-07 1.61 9.55 12 213150_at HOXA10 54.55 2.66E-10 3.78E-07 1.61 9.25 7p15-p14 71 Table 3 and 4 13 209500_x_at TNFSF13 3.85 4.68E-11 1.22E-07 1.37 9.17 17p13.1 14 204082_at PBX3 6.31 5.89E-11 1.37E-07 1.34 9.03 9q33-q34 15 205639_at AOAH 5.46 8.40E-11 1.75E-07 1.29 8.80 7p14-p12 16 228365_at LOC144402 7.86 5.32E-10 6.36E-07 1.42 8.80 12q11 17 208890_s_at PLXNB2 3.97 9.29E-11 1.82E-07 1.29 8.76 22q13.33 18 228083_at CACNA2D4 12.54 7.21 E-10 7.06E-07 1.44 8.75 12p13.33 19 201944_at HEXB 3.38 5.49E-10 6.36E-07 1.39 8.72 5q13 20 218404_at SNX10 4.18 1.56E-10 2.65E-07 1.29 8.68 7p15.2 21 204202_at KIAA1023 3.42 1.65E-10 2.65E-07 1.28 8.66 7p22.3 22 225245_x_at H2AFJ 4.99 2.65E-10 3.78E-07 1.30 8.64 12p12 23 212459_x_at SUCLG2 3.67 2.89E-11 9.04E-08 1.22 8.63 3p14.2 24 216417_x_at HOXB9 3.30 4.27E-11 1.22E-07 1.21 8.51 17q21.3 25 223562_at PARVG 3.18 5.28E-10 6.36E-07 1.25 8.36 22q13.2-q13 26 218217_at RISC 5.15 1.01 E-09 8.75E-07 1.29 8.35 17q23.1 27 203948_s_at MPO -4.44 6.12E-10 6.61 E-07 -1.23 -8.34 17q23.1 28 228058_at LOC124220 -6.10 5.49E-09 3.37E-06 -1.29 -8.28 16p13.3 29 241706_at LOC144402 5.35 8.09E-10 7.45E-07 1.22 8.17 12q11 30 201850_at CAPG 7.89 3.15E-09 2.10E-06 1.35 8.17 2cen-q24 31 224301_x_at H2AFJ 4.16 7.21 E-10 7.06E-07 1.21 8.17 12p12 32 214835_s_at SUCLG2 3.91 4.04E-10 5.27E-07 1.19 8.16 3p14.2 33 206940_s_at POU4F1 -33.65 1.84E-07 3.22E-05 -1.76 -8.14 13q21.1-q22 34 212423_at FLJ90798 5.61 1.08E-09 9.14E-07 1.22 8.14 10q22.3 35 215772_x_at SUCLG2 3.87 1.69E-10 2.65E-07 1.15 8.09 3p14.2 36 202746_at ITM2A -7.27 5.70E-08 1.67E-05 -1.39 -8.08 Xq13.3- Xq21.2 37 238756_at 4.09 1.20E-09 9.93E-07 1.21 8.08 38 204880_at MGMT -2.32 5.45E-09 3.37E-06 -1.23 -8.04 10q26 39 241370_at 3.17 2.09E-09 1.49E-06 1.20 7.94 40 224415_s_at HINT2 2.05 3.49E-10 4.75E-07 1.13 7.93 9p13.1 41 228827_at 2.83E-07 4.30E-05 -1.80 -7.92 103.62 42 225386_s_at LOC92906 6.59 6.59E-10 6.88E-07 1.14 7.90 2p22.2 43 200788_s_at PEA15 2.38 7.77E-10 7.37E-07 1.14 7.87 1q21.1 44 207839_s_at LOC51754 2.68 5.92E-10 6.61 E-07 1.12 7.85 9p13.1 45 206009_at ITGA9 -3.62 5.12E-08 1.58E-05 -1.28 -7.81 3p21.3 46 211341_at POU4F1 3.58E-07 5.05E-05 -1.74 -7.79 13q21.1-q22 150.84 47 56256_at CGI-40 2.81 1.88E-09 1.37E-06 1.14 7.77 11q23.3 48 217520_x_at LOC283683 16.90 1.17E-08 5.50E-06 1.38 7.76 15q11.2 49 219478_at WFDC1 -6.75 1.65E-07 3.09E-05 -1.36 -7.72 16q24.3 50 205774_at F12 3.18 1.69E-09 1.32E-06 1.11 7.68 5q33-qter
4.5 inv(16) versus inv(3)
# affy id HUGO name fc p q stn t Map Location 1 203949_at MPO 4.74 1.72E-13 4.54E-09 2.41 14.22 17q23.1 2 203948_s_at MPO 5.13 2.36E-12 2.08E-08 1.89 11.46 17q23.1 3 205382_s_at DF 5.65 1.05E-12 1.38E-08 1.83 11.19 19p13.3 72 Table 3 and 4 4 201497_x_at MYH11 18.46 2.05E-10 7.07E-07 2.06 10.65 16p13.13- P13.12 5 224841_x_at -1.69 2.14E-10 7.07E-07 -1.76 -10.33 6 224741_x_at -1.69 3.09E-10 9.08E-07 -1.76 -10.28 7 209365_s_at ECM1 3.28 3.37E-11 2.23E-07 1.54 9.53 1q21 8 210755_at HGF 6.18 6.96E-10 1.84E-06 1.65 9.44 7q21.1 9 228497_at FLIPT1 -3.11 8.82E-09 1.17E-05 -1.63 -9.19 1p13.1
10 205718_at ITGB7 3.07 1.91 E-10 7.07E-07 1.44 8.88 12q13.13
11 205131_x_at SCGF 4.37 1.79E-10 7.07E-07 1.40 8.73 19q13.3
12 217963_s_at NGFRAP1 -20.39 5.19E-07 1.67E-04 -1.88 -8.49 Xq22.1
13 201496_x_at MYH11 3.64 1.43E-09 3.16E-06 1.40 8.45 16p13.13- p13.12
14 222862_s_at AK5 40.65 3.10E-08 2.93E-05 1.61 8.14 1p31
15 236646_at FLJ31166 3.02 9.63E-10 2.31 E-06 1.30 8.12 12p13.31
16 226197_at 2.75 2.51 E-09 4.46E-06 1.31 8.04
17 203074_at ANXA8 1.80 2.08E-09 4.22E-06 1.30 8.04 10q11.2
18 243244_at 3.90 2.53E-09 4.46E-06 1.29 7.95
19 202605_at GUSB 2.22 4.26E-08 3.47E-05 1.30 7.70 7q21.11
20 212358_at CLIPR-59 15.49 8.58E-08 5.04E-05 1.46 7.63 19q13.12
21 201360_at CST3 3.63 4.80E-09 7.94E-06 1.22 7.62 20p11.21
22 226697_at LOC92689 2.52 6.69E-09 1.04E-05 1.22 7.58 4p14
23 201462_at KIAA0193 -5.29 3.06E-07 1.13E-04 -1.37 -7.57 7p14.3-p14.1
24 241525_at LOC200772 55.36 1.35E-07 6.48E-05 1.47 7.46 2q37.3
25 210783_x_at SCGF 4.12 8.13E-09 1.13E-05 1.20 7.46 19q13.3
26 231736_x_at MGST1 3.57 7.41 E-09 1.09E-05 1.19 7.44 12p12.3- p12.1
27 207961_x_at MYH11 15.00 1.40E-07 6.63E-05 1.43 7.42 16p13.13- p13.12
28 224441_s_at MGC14793 -3.13 8.20E-08 5.04E-05 -1.24 -7.37 6q16.3
29 205076_s_at CRA 4.21 4.89E-08 3.77E-05 1.24 7.34 1q12-q21
30 210997_at HGF 17.75 1.55E-07 6.94E-05 1.38 7.34 7q21.1
31 209975_at CYP2E1 3.46 4.33E-08 3.47E-05 1.22 7.30 10q24.3-qter
32 224918_x_at MGST1 3.27 1.58E-08 1.90E-05 1.18 7.29 12p12.3- p12.1
33 201069_at MMP2 2.83 1.26E-08 1.59E-05 1.17 7.28 16q13-q21
34 202828_s_at MMP14 5.47 1.26E-07 6.34E-05 1.29 7.25 14q11-q12
35 211709_s_at SCGF 3.22 3.48E-08 3.08E-05 1.18 7.24 19q13.3
36 202283_at SERPINF1 4.68 3.61 E-08 3.08E-05 1.18 7.18 17p13.1
37 200852_x_at GNB2 2.10 2.31 E-08 2.65E-05 1.15 7.16 7q22
38 201688_s_at TPD52 -3.31 7.77E-07 2.23E-04 -1.30 -7.14 8q21
39 219308_s_at AK5 5.75 2.20E-07 9.06E-05 1.32 7.14 1p31
40 239814_at 2.34 2.50E-08 2.75E-05 1.14 7.12
41 200985_s_at CD59 -6.95 2.61 E-06 5.15E-04 -1.42 -7.09 11p13
42 242621_at FLJ32468 1.47 2.87E-08 2.81 E-05 1.14 7.08 7q22.1
43 202185_at PL0D3 1.78 2.78E-08 2.81 E-05 1.14 7.07 7q22
44 223136_at AIG-1 -5.06 9.07E-07 2.45E-04 -1.28 -7.05 6q24.1
45 223091_x_at GL004 -1.53 1.27E-07 6.34E-05 -1.17 -7.04 2q36.3
46 223354_x_at GL004 -1.62 2.88E-07 1.09E-04 -1.21 -7.04 2q36.3
47 214797_s_at PCTK3 -2.39 4.15E-07 1.44E-04 -1.22 -7.03 1q31-q32
48 214558_at GPR12 1.53 4.99E-08 3.77E-05 1.14 7.01 13q12 73 Table 3 and 4 49 229309_at 4.49 6.27E-08 4.25E-05 1.15 7.01 50 205859 at LY86 3.30 2.78E-08 2.81 E-05 1.12 7.01 6p24.3
4.6 inv(16) versus t(15;17) affy id HUGO name fc | P ' -1 stn t Map Location 1 211990_at HLA-DPA1 12.88 7.26E-18 1.92E-13 3.35 20.08 6p21.3 2 214450_at CTSW -8.03 6.77E-13 7.14E-10 -3.05 -15.96 11q13.1 3 38487_at STAB1 -8.03 2.37E-12 1.95E-09 -3.01 -15.25 3p21.31 4 221004_s_at ITM2C -5.22 1.41 E-13 3.01 E-10 -2.58 -15.04 2q37 5 204661_at CDW52 33.75 1.67E-13 3.15E-10 2.69 14.74 1p36 6 200654_at P4HB -2.30 1.92E-15 1.27E-11 -2.31 -14.63 17q25 7 203535_at S100A9 9.01 7.53E-16 6.62E-12 2.24 14.32 1q21 8 217478_s_at HLA-DMA 7.63 2.80E-14 8.72E-11 2.35 14.21 6p21.3 9 209732_at CLECSF2 30.47 5.76E-13 6.61 E-10 2.71 14.20 12p13-p12 10 34210_at CDW52 43.85 7.27E-13 7.14E-10 2.58 13.90 1p36 11 238022_at -8.74 2.99E-12 2.25E-09 -2.41 -13.63 12 209619_at CD74 5.65 3.24E-16 4.28E-12 2.06 13.52 5q32 13 201923_at PRDX4 7.22 7.48E-14 1.79E-10 2.16 13.28 Xp22.13 14 205624_at CPA3 -9.54 1.00E-11 6.01 E-09 -2.41 -13.24 3q21-q25 15 204563_at SELL 9.35 7.30E-13 7.14E-10 2.25 13.07 1q23-q25 16 200931_s_at VCL 3.96 1.06E-14 5.62E-11 2.01 12.90 10q22.1-q23 17 231310_at 4.74 2.97E-14 8.72E-11 2.04 12.89 18 209312_x_at HLA-DRB1 8.89 3.15E-13 4.37E-10 2.06 12.62 6p21.3 19 208306_x_at HLA-DRB4 9.65 5.23E-13 6.43E-10 2.08 12.60 6p21.3 20 238365_s_at -10.74 1.01 E-10 3.36E-08 -2.50 -12.45 21 208891_at DUSP6 7.70 2.11E-14 8.72E-11 1.93 12.44 12q22-q23 22 212953_x_at CALR -2.84 2.97E-14 8.72E-11 -1.91 -12.34 19p13.3- p13.2 23 204670_x_at HLA-DRB5 6.79 3.94E-14 1.04E-10 1.91 12.25 6p21.3 24 205718_at - ITGB7 6.61 6.63E-13 7.14E-10 1.97 12.10 12q13.13 25 205453_at HOXB2 11.16 1.03E-11 6.03E-09 2.13 11.95 17q21-q22 26 205663_at PCBP3 -4.69 1.37E-11 7.52E-09 -2.01 -11.85 21q22.3 27 232617_at CTSS 8.88 1.90E-11 9.29E-09 2.15 11.78 1q21 28 207375_s_at IL15RA 4.80 1.48E-13 3.01E-10 1.84 11.77 10p15-p14 29 224583_at COTL1 5.58 3.11 E-13 4.37E-10 1.86 11.77 16q23.3 30 221059_s_at CHST6 6.80 4.13E-12 2.80E-09 1.95 11.67 16q22 31 233072_at KIAA1857 -7.47 2.04E-10 5.49E-08 -2.19 -11.60 9q34 32 229168_at DKFZp434K0621 -6.73 3.74E-10 8.88E-08 -2.36 -11.59 5q35.3 33 208982_at PECAM1 4.84 2.17E-12 1.85E-09 1.88 11.55 17q23 34 224839_s_at GPT2 -9.02 4.23E-11 1.75E-08 -1.95 -11.41 16q12.1 35 202803_s_at ITGB2 5.43 5.36E-13 6.43E-10 1.72 11.07 21 q22.3 36 223280_x_at MS4A6A 24.98 9.94E-11 3.36E-08 2.11 11.04 11q12.1 37 201496_x_at MYH11 10.61 1.13E-11 6.47E-09 1.81 10.98 16p13.13- p13.12 38 211991_s_at HLA-DPA1 25.17 9.82E-11 3.36E-08 2.05 10.97 6p21.3 39 204150_at STAB1 -9.71 1.08E-09 2.11 E-07 -2.26 -10.94 3p21.31 74 I l able "ό an 40 208689_s_at RPN2 -1.75 1.91 E-13 3.36E-10 -1.66 -10.90 20q12-q13.1 41 220798_x_at FLJ11535 -3.81 7.69E-11 2.82E-08 -1.84 -10.89 19p13.3 42 201497_x_at MYH11 28.44 1.48E-10 4.48E-08 2.16 10.88 16p13.13- p13.12 43 202917_s_at S100A8 3.19 3.79E-13 5.01 E-10 1.66 10.85 1q21 44 241742_at PRAM-1 11.60 1.23E-10 3.81 E-08 1.97 10.76 19p13.2 45 228046_at LOC152485 3.03 5.49E-12 3.54E-09 1.72 10.76 4q31.1 46 226878_at 4.19 1.90E-11 9.29E-09 1.77 10.75 47 238604_at 3.63 2.30E-13 3.79E-10 1.62 10.71 48 213779_at LOC129080 -6.64 9.66E-10 1.96E-07 -2.04 -10.68 22q12.1 49 224356_x_at MS4A6A 25.23 2.22E-10 5.74E-08 2.06 10.62 11q12.1 50 217897_at FXYD6 3.03 3.34E-11 1.44E-08 1.77 10.62 11 q23.3
4.7 inv(16) versus t(8;21)
# affy id HUGO name fc | P < q stn t Map Location 1 207075_at CIAS1 6.59 1.58E-12 1.75E-08 2.20 12.68 1q44 2 208890_s_at PLXNB2 5.12 3.17E-13 7.15E-09 1.97 12.18 22q13.33 3 205453_at HOXB2 12.87 7.80E-12 3.24E-08 2.16 12.11 17q21-q22 4 205419_at EBI2 7.52 3.29E-12 2.73E-08 2.01 11.90 13q32.2 5 205718_at ITGB7 6.71 4.31 E-13 7.15E-09 1.91 11.89 12q13.13 6 224764_at ARHGAP10 8.78 1.26E-11 4.63E-08 2.02 11.59 10 7 201497_x_at MYH11 26.12 1.56E-10 2.16E-07 2.14 10.85 16p13.13- p13.12 8 201496_x_at MYH11 9.21 1.72E-11 5.70E-08 1.80 10.83 16p13.13- p13.12 9 224049_at KCNK17 4.64 1.11 E-10 1.77E-07 1.92 10.69 6p21.1 10 200665_s_at SPARC 4.28 7.71E-12 3.24E-08 1.63 10.32 5q31.3-q32 11 224724_at SULF2 26.61 4.15E-10 4.05E-07 1.99 10.28 20q12-13.2 12 218236_s_at PRKCN 4.73 5.10E-12 3.10E-08 1.59 10.16 2p21 13 218795_at ACP6 -4.42 3.10E-10 3.26E-07 -1.68 -10.03 1q21 14 201425_at ALDH2 7.98 2.08E-10 2.50E-07 1.72 10.03 12q24.2 15 201944_at HEXB 2.26 4.28E-11 1.01 E-07 1.57 9.82 5q13 16 201887_at IL13RA1 4.99 3.14E-10 3.26E-07 1.63 9.67 Xq24 17 201360_at CST3 5.36 1.21 E-10 1.83E-07 1.57 9.65 20p11.21 18 238604_at 3.10 5.61 E-12 3.10E-08 1.46 9.56 19 209365_s_at ECM1 3.14 3.60E-11 9.96E-08 1.49 9.52 1q21 20 201596_x_at KRT18 7.58 2.11E-10 2.50E-07 1.56 9.52 12q13 21 202670_at MAP2K1 3.60 5.03E-10 4.58E-07 1.59 9.45 15q22.1- q22.33 22 203320_at LNK 3.09 1.34E-10 1.94E-07 1.50 9.37 12q24 23 210314_x_at TNFSF13 4.88 2.77E-10 3.06E-07 1.53 9.36 17p13.1 24 209500_x_at TNFSF13 4.05 4.42E-10 4.19E-07 1.55 9.34 17p13.1 25 221841_s_at 4.04 3.60E-11 9.96E-08 1.42 9.21 26 235359_at 2.91 1.88E-10 2.49E-07 1.47 9.20 27 223249_at CLDN12 3.53 1.06E-10 1.77E-07 1.44 9.16 7q21 28 218217_at RISC 3.35 1.12E-10 1.77E-07 1.43 9.10 17q23.1 29 201739_at SGK 4.42 4.17E-11 1.01 E-07 1.40 9.07 6q23 75 I able ana 4 30 229309_at 11.50 3.64E-09 1.89E-06 1.64 9.01 31 240572_s_at 3.26 9.26E-11 1.77E-07 1.39 8.95 32 208683_at CAPN2 3.21 9.71 E-11 1.77E-07 1.38 8.92 1q41-q42 33 225602_at C9orf19 2.86 5.10E-11 1.13E-07 1.36 8.90 9p13-p12 34 226818_at LOC219972 11.01 2.61 E-09 1.63E-06 1.54 8.89 11q12.1 35 220974_x_at BA108L7.2 4.78 3.85E-10 3.87E-07 1.39 8.79 10q24.31 36 229383_at 5.01 3.55E-09 1.87E-06 1.52 8.77 37 212459_x_at SUCLG2 3.54 8.98E-11 1.77E-07 1.34 8.72 3p14.2 38 205859_at LY86 3.60 1.34E-09 1.01 E-06 1.43 8.71 6p24.3 39 211084_x_at PRKCN 4.82 2.26E-10 2.58E-07 1.33 8.60 2p21 40 236738_at 6.52 1.66E-09 1.20E-06 1.40 8.60 41 217849_s_at CDC42BPB 4.85 2.02E-10 2.50E-07 1.32 8.59 14q32.3 42 205330_at MN1 9.06 1.06E-08 4.35E-06 1.56 8.52 22q12.1 43 204057_at ICSBP1 4.27 5.50E-09 2.68E-06 1.44 8.46 16q24.1 44 228415_at AP1S2 2.82 2.29E-09 1.52E-06 1.33 8.30 Xp22.31 45 202283_at SERPINF1 8.45 2.79E-09 1.65E-06 1.34 8.29 17p13.1 46 226841_at LOC219972 12.54 1.86E-08 6.29E-06 1.51 8.26 11q12.1 47 226137_at 3.27 4.82E-09 2.42E-06 1.36 8.26 48 208033_s_at ATBF1 3.76 1.34E-09 1.01 E-06 1.30 8.24 16q22.3- q23.1 49 233555_s_at SULF2 17.48 2.64E-08 8.12E-06 1.58 8.19 20q12-13.2 50 205076_s_at CRA 5.49 1.56E-08 5.96E-06 1.44 8.19 1q12-q21
4.8 inv(3) versus t( 15; 17)
# affy id HUGO name fc p q stn t Map Location 1 212953_x_at CALR -5.95 2.17E-14 5.07E-11 -3.69 -18.88 19p13.3- p13.2 2 205382_s_at DF -12.24 2.37E-15 7.12E-12 -3.43 -18.68 19p13.3 3 203948_s_at MPO -9.29 4.98E-19 1.05E-14 -3.14 -18.5717q23.1 4 203949_at MPO -6.22 1.52E-17 1.60E-13 -3.05 -17.8217q23.1 5 200654_at P4HB -3.78 4.67E-17 3.27E-13 -2.71 -16.0317q25 6 214450_at CTSW -8.62 1.58E-13 2.89E-10 -2.90 -15.6711q13.1 7 231736_x_at MGST1 -6.90 6.57E-16 2.30E-12 -2.57 -15.0912p12.3- p12.1 8 224918_x_at MGST1 -6.02 2.58E-16 1.15E-12 -2.54 -15.0212p12.3- p12.1 9 206871_at ELA2 -6.28 2.73E-16 1.15E-12 -2.54 -15.0019p13.3 10 214575_s_at AZU1 -12.19 2.49E-13 3.73E-10 -2.58 -14.3419p13.3 11 205624_at CPA3 -21.54 5.79E-12 5.79E-09 -2.85 -14.333q21-q25 12 208689_s_at RPN2 -2.77 3.65E-15 9.58E-12 -2.43 -14.2720q12-q13.1 13 238022_at -8.14 1.08E-12 1.33E-09 -2.28 -12.89 14 38487_at STAB1 -5.21 5.94E-13 8.31E-10 -2.23 -12.763p21.31 15 221004_s_at ITM2C -4.36 8.93E-14 1.88E-10 -2.12 -12.492q37 16 217716_s_at SEC61A1 -2.51 1.65E-13 2.89E-10 -2.09 -12.253q21.3 17 221739_at IL27w -2.24 2.31 E-13 3.73E-10 -2.06 -12.1119p13.3 18 233072_at KIAA1857 -10.04 1.05E-10 5.14E-08 -2.37 -12.069q34 19 208852 s at CANX -2.94 3.24E-12 3.78E-09 -2.07 -11.865q35 76 Table 3 and 4 20 220798_x_at FLJ11535 -5.26 7.78E-12 6.81 E-09 -2.05 -11.62 19p13.3 21 217225_x_at LOC283820 -2.41 9.52E-13 1.25E-09 -1.94 -11.43 16p13.13 22 208730_x_at RAB2 2.53 8.63E-10 3.12E-07 2.18 11.42 8q12.1 23 203675_at NUCB2 -3.92 6.96E-12 6.65E-09 -2.00 -11.42 11p15.1-p14 24 201004_at SSR4 -2.77 1.64E-11 1.15E-08 -2.00 -11.33 Xq28 25 210788_s_at retSDR4 -2.65 7.69E-12 6.81 E-09 -1.95 -11.22 14q22.3 26 202759_s_at AKAP2 -4.78 2.58E-11 1.69E-08 -1.98 -11.15 9q31-q33 27 209619_at CD74 4.57 1.47E-11 1.14E-08 1.92 11.07 5q32 28 214315_x_at CALR -3.14 2.25E-11 1.52E-08 -1.93 -11.00 19p13.3- p13.2 29 229168_at DKFZp434K0621 -5.62 4.18E-10 1.72E-07 -2.12 -10.99 5q35.3 30 211990_at HLA-DPA1 12.02 1.70E-08 3.31 E-06 2.38 10.92 6p21.3 31 214797_s_at PCTK3 6.22 2.95E-09 8.48E-07 2.12 10.91 1q31-q32 32 211709_s_at SCGF -5.08 3.77E-12 3.96E-09 -1.80 -10.65 19q13.3 33 200068 s at - HG - CANX -1.76 3.59E-12 3.96E-09 -1.79 -10.61 5q35 U133A 34 206914_at CRTAM 6.82 3.01 E-09 8.54E-07 1.99 10.50 11 q22-q23 35 204897_at PTGER4 5.48 3.25E-10 1.37E-07 1.87 10.44 5p13.1 36 221253_s_at MGC3178 -3.45 5.95E-11 3.62E-08 -1.81 -10.36 6p24.3 37 225010_at D10S170 2.56 2.69E-11 1.71 E-08 1.77 10.33 10q21 38 210140_at CST7 -8.79 1.17E-09 4.09E-07 -1.98 -10.32 20p11.21 39 226905_at -1.96 8.40E-11 4.20E-08 -1.78 -10.24 40 200652_at SSR2 -1.91 1.02E-11 8.61 E-09 -1.73 -10.22 1q21-q23 41 33323_r_at SFN 1.93 1.07E-11 8.68E-09 1.73 10.21 1p35.3 42 227353_at EVER2 5.28 1.34E-08 2.75E-06 2.02 10.17 17q25.3 43 224839_s_at GPT2 -6.13 8.34E-11 4.20E-08 -1.77 -10.15 16q12.1 44 200068 s at - HG - CANX -1.67 1.62E-11 1.15E-08 -1.72 -10.14 5q35 U133B 45 209215_at TETRAN -3.38 1.52E-11 1.14E-08 -1.72 -10.14 4p16.3 46 205614_x_at MST1 -8.62 3.49E-09 9.53E-07 -2.00 -9.99 3p21 47 241383_at -4.56 2.13E-09 6.47E-07 -1.87 -9.85 48 214317_x_at RPS9 2.30 1.38E-09 4.55E-07 1.77 9.82 19q13.4 49 202487_s_at H2AV -2.25 6.02E-11 3.62E-08 -1.64 -9.66 7p13 50 204661_at CDW52 22.88 1.06E-07 1.35E-05 2.16 9.63 1p36
4.9 inv(3) versus t(8;21)
# affy id HUGO name fc P q stn t Map Location 1 203949_at MPO -5.73 1.58E-13 3.73E-09 -2.14 -12.41 17q23.1 2 211084_x_at PRKCN 6.08 3.25E-10 1.92E-06 1.92 10.59 2p21 3 225010_at D10S170 2.96 1.16E-11 1.38E-07 1.78 10.37 10q21 4 233955_x_at HSPC195 5.19 3.37E-08 8.86E-05 2.18 10.19 5q31.3 5 203948_s_at MPO -6.82 1.36E-10 1.07E-06 -1.74 -9.93 17q23.1 6 217963_s_at NGFRAP1 29.01 4.74E-07 3.74E-04 2.04 8.67 Xq22.1 7 224516_s_at HSPC195 5.87 5.57E-07 3.79E-04 1.92 8.45 5q31.3 8 219478_at WFDC1 -12.35 6.15E-08 1.28E-04 -1.68 -8.45 16q24.3 9 217226_s_at BA108L7.2 3.53 7.38E-08 1.28E-04 1.58 8.38 10q24.31 10 231180 at -2.35 2.92E-09 1.38E-05 -1.42 -8.23 77 Table a ana 4 11 201281_at ADRM1 -2.17 1.21 E-08 4.62E-05 -1.45 -8.15 20q13.33 12 212423_at FLJ90798 4.18 7.41 E-08 1.28E-04 1.49 8.07 10q22.3 13 222996_s_at HSPC195 4.31 1.08E-06 4.79E-04 1.79 7.98 5q31.3 14 228827_at -95.46 2.85E-07 2.93E-04 -1.78 -7.91 15 230259_at -1.91 2.21 E-08 6.52E-05 -1.37 -7.77 16 213716_s_at SECTM1 5.01 2.54E-07 2.86E-04 1.44 7.68 17q25 17 211709_s_at SCGF -3.55 1.37E-08 4.62E-05 -1.30 -7.56 19q13.3 18 202759_s_at AKAP2 -4.91 2.29E-07 2.71 E-04 -1.45 -7.56 9q31-q33 19 219165_at PDLIM2 3.79 6.33E-07 4.00E-04 1.48 7.55 8p21.2 20 206478_at KIAA0125 23.32 2.67E-06 8.31 E-04 1.89 7.54 14q32.33 21 205529_s_at CBFA2T1 -13.48 6.51 E-07 4.00E-04 -1.63 -7.44 8q22 22 212895_s_at ABR 3.03 3.97E-07 3.50E-04 1.38 7.38 17p13.3 23 223534_s_at RPS6KL1 -2.20 8.42E-08 1.33E-04 -1.31 -7.37 14q24.2 24 212953_x_at CALR -2.47 3.99E-07 3.50E-04 -1.42 -7.33 19p13.3- p13.2 25 206295_at IL18 3.69 1.85E-06 6.95E-04 1.52 7.33 11q22.2- q22.3 26 202006_at PTPN12 2.76 6.85E-07 4.00E-04 1.39 7.29 7q11.23 27 220974_x_at BA108L7.2 4.34 5.65E-07 3.79E-04 1.37 7.27 10q24.31 28 201243_s_at ATP1B1 5.21 2.00E-06 7.03E-04 1.50 7.27 1q22-q25 29 201938_at CDK2AP1 2.10 7.57E-08 1.28E-04 1.27 7.26 12q24.31 30 207839_s_at LOC51754 3.16 2.14E-07 2.66E-04 1.30 7.24 9p13.1 31 203820_s_at K0C1 3.93 2.73E-06 8.37E-04 1.53 7.19 7p11 32 202887_s_at RTP801 4.32 1.72E-06 6.79E-04 1.44 7.17 10pter- q26.12 33 215051_x_at AIF1 2.69 1.90E-07 2.49E-04 1.28 7.17 6p21.3 34 214042_s_at RPL22 1.48 7.74E-07 4.16E-04 1.35 7.15 1p36.3-p36.2 35 227620_at 3.79 3.71 E-07 3.50E-04 1.27 7.03 36 210150_s_at LAMA5 -4.17 5.29E-07 3.79E-04 -1.31 -7.01 20q13.2- q13.3 37 230659_at KIAA0212 -2.09 5.37E-07 3.79E-04 -1.30 -6.99 3p26.1 38 221773_at 3.81 8.38E-07 4.31 E-04 1.30 6.99 39 226865_at 8.49 5.84E-06 1.21E-03 1.64 6.98 40 242621_at FLJ32468 -1.58 2.69E-07 2.90E-04 -1.24 -6.95 7q22.1 41 229406_at -11.72 1.19E-06 4.98E-04 -1.39 -6.94 42 214317_x_at RPS9 2.15 7.51 E-08 1.28E-04 1.19 6.93 19q13.4 43 213908_at 3.96 2.61 E-06 8.24E-04 1.38 6.92 44 204494_s_at DKFZP434H132 4.90 6.20E-06 1.21E-03 1.56 6.89 15q22.33 45 214807_at 2.91 2.89E-06 8.66E-04 1.34 6.80 46 220377_at C14orf110 239.90 8.80E-06 1.40E-03 1.75 6.79 14q32.33 47 221458_at HTR1 F 2.55 2.14E-06 7.23E-04 1.30 6.77 3p12 48 227279_at MGC15737 3.22 4.36E-06 1.08E-03 1.38 6.76 Xq22.1 49 206871 _at ELA2 -5.10 6.92E-07 4.00E-04 -1.22 -6.69 19p13.3 50 235199 at 2.76 1.11 E-06 4.79E-04 1.22 6.68
4.10 t(15;17) versus t(8;21)
# affy id HUGO name fc stn Map Location 78 Table 3 and 4 1 214450_at CTSW 28.73 1.65E-13 4.t>yt-09 3.58 17.73 11q13.1 2 38487_at STAB1 19.69 4.77E-13 4.59E-09 3.26 16.49 3p21.31 3 209732_at CLECSF2 -30.76 2.95E-12 1.46E-08 -3.39 -16.10 12p13-p12 4 211990_at HLA-DPA1 -10.92 1.76E-11 5.09E-08 -2.53 -13.40 6p21.3 5 224839_s_at GPT2 12.98 6.62E-11 1.19E-07 2.37 12.32 16q12.1 6 212509_s_at 10.31 9.35E-11 1.59E-07 2.37 12.20 7 204150_at STAB1 21.33 3.55E-10 4.10E-07 2.36 11.58 3p21.31 8 201596_x_at KRT18 20.06 3.29E-10 3.96E-07 2.28 11.50 12q13 9 221004_s_at ITM2C 3.37 4.65E-13 4.59E-09 1.86 11.42 2q37
10 205349_at GNA15 3.53 3.47E-11 8.35E-08 2.00 11.42 19p13.3
11 205663_at PCBP3 4.49 9.95E-12 3.59E-08 1.92 11.33 21 q22.3
12 226878_at -5.52 8.96E-10 7.61 E-07 -2.06 -10.80
13 212953_x_at CALR 2.41 1.19E-12 8.57E-09 1.74 10.78 19p13.3- p13.2
14 227326_at 5.43 2.89E-10 3.63E-07 1.89 10.58
15 217716_s_at SEC61A1 2.09 3.73E-12 1.54E-08 1.70 10.48 3q21.3
16 228113_at STAT3 -5.12 5.53E-10 5.50E-07 -1.86 -10.38 17q21
17 200986_at SERP1NG1 9.81 1.47E-09 1.09E-06 1.98 10.34 11q12-q13.1
18 208689_s_at RPN2 1.79 3.03E-12 1.46E-08 1.63 10.17 20q12-q13.1
19 217478_s_at HLA-DMA -5.35 6.89E-10 6.42E-07 -1.81 -10.15 6p21.3
20 204316_at RGS10 -2.45 1.99E-10 2.67E-07 -1.73 -10.10 10q25
21 209021_x_at KIAA0652 4.43 3.36E-11 8.35E-08 1.61 9.83 11p11.12
22 205614_x_at MST1 7.54 3.75E-09 2.30E-06 1.83 9.69 3p21
23 209619_at CD74 -4.60 1.28E-10 1.95E-07 -1.60 -9.66 5q32
24 200953_s_at CCND2 2.70 4.02E-10 4.30E-07 1.65 9.66 12p13
25 208852_s_at CANX 2.32 6.39E-11 1.19E-07 1.57 9.60 5q35
26 208826_x_at HINT1 1.43 5.89E-11 1.19E-07 1.56 9.58 5q31.2
27 201522_x_at SNRPN -3.65 1.70E-11 5.09E-08 -1.53 -9.54 15q12
28 201136_at PLP2 2.76 2.03E-10 2.67E-07 1.56 9.41 Xp11.23
29 201137_s_at HLA-DPB1 -13.39 1.86E-08 7.79E-06 -1.93 -9.37 6p21.3
30 201425_at ALDH2 5.16 1.10E-09 8.76E-07 1.61 9.35 12q24.2
31 204670_x_at HLA-DRB5 -5.72 8.74E-10 7.61 E-07 -1.58 -9.30 6p21.3
32 201952_at ALCAM 4.64 2.50E-09 1.76E-06 1.65 9.30 3q13.1
33 211991_s_at HLA-DPA1 -17.00 2.54E-08 9.11 E-06 -1.85 -9.13 6p21.3
34 209312_x_at HLA-DRB1 -6.80 5.84E-09 3.18E-06 -1.63 -9.09 6p21.3
35 238022_at 4.06 6.47E-11 1.19E-07 1.46 9.09
36 211474_s_at SERPINB6 -5.69 1.90E-08 7.82E-06 -1.74 -9.06 6p25
37 223321_s_at FGFRL1 3.74 4.94E-09 2.89E-06 1.61 9.02 4p16
38 201894_s_at DCN 2.05 1.13E-10 1.81 E-07 1.42 8.86 12q13.2
39 208885_at LCP1 2.18 1.50E-10 2.16E-07 1.42 8.85 13q14.3
40 201923_at PRDX4 -5.83 1.40E-08 6.42E-06 -1.61 -8.82 Xp22.13
41 209344_at TPM4 6.87 2.27E-08 8.69E-06 1.69 8.80 19p13.1
42 227353_at EVER2 -3.83 4.90E-09 2.89E-06 -1.52 -8.79 17q25.3
43 202732_at PKIG 2.65 2.70E-09 1.79E-06 1.49 8.74 20q12-q13.1
44 208306_x_at HLA-DRB4 -7.05 1.62E-08 7.08E-06 -1.57 -8.69 6p21.3
45 55093_at CSGIcA-T 1.87 6.61 E-10 6.36E-07 1.41 8.65 7q36.1
46 201360_at CST3 4.20 2.73E-09 1.79E-06 1.45 8.61 20p11.21
47 221799_at CSGIcA-T 2.51 3.90E-10 4.30E-07 1.38 8.59 7q36.1 79 Table 3 and 4
48 201581_at DJ971N18.2 2.54 2.69E-09 1.79E-06 1.44 8.58 20p12
49 207721_x_at HINT1 1.55 5.39E-10 5.50E-07 1.38 8.52 5q31.2
50 205035 at CTDP1 2.57 1.34E-08 6.42E-06 1.51 8.51 18q23

Claims

Claims
1. A method for distinguishing AML subtype AML_inv(3) from other AML subtypes in a sample, the method comprising determining the expression level of markers selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4, wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.1 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.1 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from all other subtypes, and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.2 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.2 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.3 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.3 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.4 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.4 having a positive fc value, is indicative for the presence of AML_normal when AML iormal is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.5 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.5 having a positive fc value, is indicative for the presence of AML_t( 15 ; 17) when AML_t( 15 ; 17) is distinguished from all other subtypes , and or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.6 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 1.6 having a positive fc value, is indicative for the presence of AML_t(8;21) when AML_t(8;21) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.1 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.1 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_inv(l 6), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.2 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.2 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_inv(3), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.3 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.3 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_normal, and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.4 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.4 having a positive fc value, is indicative for the presence of AML_11 q23 when AML_11 q23 is distinguished from AML_t(15;17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.5 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.5 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_t(8;21), and or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.6 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.6 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML_inv(3), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.7 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.7 having a positive fc value, is indicative for the presence of AML_inv( 16) when AML_inv( 16) is distinguished from AMLjtiormal, and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.8 having a negative fc value, and or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.8 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML_t(l 5 ; 17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.9 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.9 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML_t(8 ;21 ), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.10 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.10 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from AML_normal, and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.11 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.11 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from AML_t(15;17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.12 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.12 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from AML_t(8;21), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.13 having a negative fc value, and or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.13 having a positive fc value, is indicative for the presence of AML_normal when AMLjnormal is distinguished from AML_t(l 5 ; 17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.14 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.14 having a positive fc value, is indicative for the presence of AML_normal when AML_normal is distinguished from AML_t(8;21), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.15 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 2.15 having a positive fc value, is indicative for the presence of AML_t(15;17) when AML_t(15;17) is distinguished from AML_t(8;21), and or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.1 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.1 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from all other subtypes , and or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.2 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.2 having a positive fc value, is indicative for the presence of AML_inv( 16) when AML_inv( 16) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.3 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.3 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.4 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.4 having a positive fc value, is indicative for the presence of AML_t(15;17) when AML_t(15;17) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.5 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 3.5 having a positive fc value, is indicative for the presence of AML_t(8;21) when AML_t(8;21) is distinguished from all other subtypes , and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.1 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.1 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_inv(16), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.2 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.2 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_inv(3), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.3 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.3 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_t(15;17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.4 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.4 having a positive fc value, is indicative for the presence of AML_1 lq23 when AML_1 lq23 is distinguished from AML_t(8;21), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.5 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.5 having a positive fc value, is indicative for the presence of AML_inv( 16) when AML_inv( 16) is distinguished from AML_inv(3), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.6 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.6.having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML_t(l 5; 17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.7 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.7 having a positive fc value, is indicative for the presence of AML_inv(16) when AML_inv(16) is distinguished from AML_t(8;21 ), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.8 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.8 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from AML_t(15;17), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.9 having a negative fc value, and or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.9 having a positive fc value, is indicative for the presence of AML_inv(3) when AML_inv(3) is distinguished from AML_t(8;21), and/or wherein a lower expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.10 having a negative fc value, and/or a higher expression of at least one polynucleotide defined by at least one of the numbers 1 to 50 of Table 4.10 having a positive fc value, is indicative for the presence of AML_t(15;17)when AML_t(15;17)is distinguished from AML_t(8;21).
2. The method according to claim 1 wherein the polynucleotide is labelled.
3. The method according to claim 1 or 2, wherein the label is a luminescent, preferably a fluorescent label, an enzymatic or a radioactive label.
4. The method according at least one of the claims 1-3, wherein the expression level of at least two, preferably of at least ten, more preferably of at least 25, most preferably of 50 of the markers of at least one of the Tables 1-4 is determined.
5. The method according to at least one of the claims 1-4, wherein the expression level of markers expressed lower in a first subtype than in at least one second subtype, which differs from the first subtype, is at least 5 %, 10% or 20%, more preferred at least 50% or may even be 75% or 100%, i.e. 2-fold lower, preferably at least 10-fold, more preferably at least 50- fold, and most preferably at least 100-fold lower in the first subtype.
6. The method according to at least one of the claims 1-4, wherein the expression level of markers expressed higher in a first subtype than in at least one second subtype, which differs from the first subtype, is at least 5 %, 10% or 20%, more preferred at least 50% or may even be 75% or 100%, i.e. 2-fold higher, preferably at least 10-fold, more preferably at least 50- fold, and most preferably at least 100-fold higher in the first subtype.
7. The method according to at least one of the claims 1-6, wherein the sample is from an individual having AML.
8. The method according to at least one of the claims 1-7, wherein at least one polynucleotide is in the form of a transcribed polynucleotide, or a portion thereof.
9. The method according to claim 8, wherein the transcribed polynucleotide is a mRNA or a cDNA.
10. The method according to claim 8 or 9, wherein the determining of the expression level comprises hybridizing the transcribed polynucleotide to a complementary polynucleotide, or a portion thereof, under stringent hybridization conditions.
11. The method according to at least one of the claims 1-7, wherein at least one polynucleotide is in the form of a polypeptide, or a portion thereof.
12. The method according to at least one of the claims 8, 9 or 12, wherein the determining of the expression level comprises contacting the polynucleotide or the polypeptide with a compound specifically binding to the polynucleotide or the polypeptide.
13. The method according to claim 12, wherein the compound is an antibody, or a fragment thereof.
14. The method according to at least one of the claims 1-13, wherein the method is carried out on an array.
15. The method according to at least one of the claims 1-14, wherein the method is carried out in a robotics system.
16. The method according to at least one of the claims 1-15, wherein the method is carried out using microfluidics.
17. Use of at least one marker as defined in at least one of the claims 1-3 for the manufacturing of a diagnostic for distinguishing AML subtype AML_inv(3) from other AML subtypes.
18. The use according to claim 17 for distinguishing AML subtype AML_inv(3) from other AML subtypes in an individual having AML.
19. A diagnostic kit containing at least one marker as defined in at least one of the claims 1-3 for distinguishing AML subtype AML_inv(3) from other AML subtypes, in combination with suitable auxiliaries.
20. The diagnostic kit according to claim 19, wherein the kit contains a reference for the AML subtype AML_inv(3) and/or any other AML subtype.
21. The diagnostic kit according to claim 20, wherein the reference is a sample or a data bank.
22. An apparatus for distinguishing AML subtype AML_inv(3) from other AML subtypes in a sample containing a reference data bank.
23. The apparatus according to claim 22, wherein the reference data bank is obtainable by comprising (a) compiling a gene expression profile of a patient sample by determining the expression level of at least one marker selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4, and (b) classifying the gene expression profile by means of a machine learning algorithm.
24. The apparatus according to claim 23, wherein the machine learning algorithm is selected from the group consisting of Weighted Voting, K- Nearest Neighbors, Decision Tree Induction, Support Vector Machines, and Feed-Forward Neural Networks, preferably Support Vector Machines.
25. The apparatus according to at least one of the claims 22-24, wherein the apparatus contains a control panel and/or a monitor.
26. A reference data bank for distinguishing AML subtype AML_inv(3) from other AML subtypes obtainable by comprising (a) compiling a gene expression profile of a patient sample by determining the expression level of at least one marker selected from the markers identifiable by their Affymetrix Identification Numbers (affy id) as defined in Tables 1, 2, 3, and/or 4, and (b) classifying the gene expression profile by means of a machine learning algorithm.
27. The reference data bank according to claim 26, wherein the reference data bank is backed up and/or contained in a computational memory chip.
EP04797588A 2003-11-04 2004-11-04 METHOD FOR DISTINGUISHING AML SUBTYPE INV(3)(q21q26)/t(3;3)(q21q26) FROM OTHER AML SUBTYPES Withdrawn EP1682899A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP04797588A EP1682899A2 (en) 2003-11-04 2004-11-04 METHOD FOR DISTINGUISHING AML SUBTYPE INV(3)(q21q26)/t(3;3)(q21q26) FROM OTHER AML SUBTYPES

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP03025345 2003-11-04
EP04797588A EP1682899A2 (en) 2003-11-04 2004-11-04 METHOD FOR DISTINGUISHING AML SUBTYPE INV(3)(q21q26)/t(3;3)(q21q26) FROM OTHER AML SUBTYPES
PCT/EP2004/012461 WO2005045438A2 (en) 2003-11-04 2004-11-04 METHOD FOR DISTINGUISHING AML SUBTYPE INV(3)(q21q26)/t(3;3)(q21q26) FROM OTHER AML SUBTYPES

Publications (1)

Publication Number Publication Date
EP1682899A2 true EP1682899A2 (en) 2006-07-26

Family

ID=34560152

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04797588A Withdrawn EP1682899A2 (en) 2003-11-04 2004-11-04 METHOD FOR DISTINGUISHING AML SUBTYPE INV(3)(q21q26)/t(3;3)(q21q26) FROM OTHER AML SUBTYPES

Country Status (2)

Country Link
EP (1) EP1682899A2 (en)
WO (1) WO2005045438A2 (en)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6647341B1 (en) * 1999-04-09 2003-11-11 Whitehead Institute For Biomedical Research Methods for classifying samples and ascertaining previously unknown classes
EP1308522A1 (en) * 2001-11-05 2003-05-07 Haferlach, Torsten, PD Dr. Dr. Novel genetic markers for leukemias
EP1470247A2 (en) * 2001-11-05 2004-10-27 Deutsches Krebsforschungszentrum Novel genetic markers for leukemias

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005045438A3 *

Also Published As

Publication number Publication date
WO2005045438A2 (en) 2005-05-19
WO2005045438A3 (en) 2005-08-11

Similar Documents

Publication Publication Date Title
US20070198198A1 (en) Methods and apparatuses for diagnosing AML and MDS
EP1470247A2 (en) Novel genetic markers for leukemias
US20090118132A1 (en) Classification of Acute Myeloid Leukemia
WO2006048266A2 (en) Gene expression profiling of leukemias with mll gene rearrangements
US20070148648A1 (en) Method for distinguishing who classified aml subtypes
WO2005045434A2 (en) Method for distinguishing aml subtypes with recurring genetic aberrations
WO2005045438A2 (en) METHOD FOR DISTINGUISHING AML SUBTYPE INV(3)(q21q26)/t(3;3)(q21q26) FROM OTHER AML SUBTYPES
US20070207459A1 (en) Method For Distinguishing Immunologically Defined All Subtype
US20070292970A1 (en) Method for Distinguishing Aml-Specific Flt3 Length Mutations From Tkd Mutations
WO2005043162A2 (en) Method for distinguishing mll-ptd-positive aml from other aml subtypes
US20070099190A1 (en) Method for distinguishing leukemia subtypes
WO2005043164A2 (en) Method for distinguishing cbf-positive aml subtypes from cbf-negative aml subtypes
US20070275380A1 (en) Method for Distinguishing Aml Subtypes With Aberrant and Prognostically Intermediate Karyotypes
US20070212734A1 (en) Method for Distinguishing T(11Q23)/Mll-Positive Leukemias From t(11Q23)/Mll Negative Leukemia
US20070128607A1 (en) Method for distinguishing aml subtypes with different gene dosages
US20070122814A1 (en) Methods for distinguishing prognostically definable aml
EP1815012A2 (en) Classifying leukemia with translocation (9;22)

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20060606

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LU MC NL PL PT RO SE SI SK TR

DAX Request for extension of the european patent (deleted)
17Q First examination report despatched

Effective date: 20071016

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20090806