WO2005116850A9 - Expression differentielle de marqueurs dans le cancer de l'ovaire - Google Patents

Expression differentielle de marqueurs dans le cancer de l'ovaire

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Publication number
WO2005116850A9
WO2005116850A9 PCT/IB2005/002555 IB2005002555W WO2005116850A9 WO 2005116850 A9 WO2005116850 A9 WO 2005116850A9 IB 2005002555 W IB2005002555 W IB 2005002555W WO 2005116850 A9 WO2005116850 A9 WO 2005116850A9
Authority
WO
WIPO (PCT)
Prior art keywords
pea
amino acid
amino acids
node
homologous
Prior art date
Application number
PCT/IB2005/002555
Other languages
English (en)
Other versions
WO2005116850A2 (fr
WO2005116850A3 (fr
Inventor
Gad S Cojocaru
Sarah Pollock
Zurit Levine
Alexander Diber
Guy Kol
Amir Toporik
Rotem Sorek
Dvir Dahary
Michal Ayalon-Soffer
Pinchas Akiva
Amit Novik
Yossi Cohen
Osnat Sella-Tavor
Shira Walach
Shirley Sameah-Greenwald
Ronen Shemesh
Maxim Shklar
Original Assignee
Compugen Ltd
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 Compugen Ltd filed Critical Compugen Ltd
Priority to AU2005248530A priority Critical patent/AU2005248530A1/en
Priority to EP05780004A priority patent/EP1721257A2/fr
Priority to CA002554703A priority patent/CA2554703A1/fr
Priority claimed from US11/043,806 external-priority patent/US7368548B2/en
Publication of WO2005116850A2 publication Critical patent/WO2005116850A2/fr
Publication of WO2005116850A9 publication Critical patent/WO2005116850A9/fr
Publication of WO2005116850A3 publication Critical patent/WO2005116850A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/112—Disease subtyping, staging or classification

Definitions

  • the present invention is related to novel nucleotide and protein sequences that are diagnostic markers for ovarian cancer, and assays and methods of use thereof.
  • Ovarian cancer causes more deaths than any other cancer of the female reproductive system.
  • An estimated 25,580 new cases will be diagnosed during 2004 in the United States, and approximately 16,090 of these women will die of the disease.
  • 70% to 80% of patients will ultimately succumb to disease that is diagnosed in iate stages.
  • ovarian cancer is diagnosed in stage I, more than 90% of patients can be cured with conventional surgery and chemotherapy.
  • stage I Detection of a greater fraction of ovarian cancers at an early stage might significantly affect survival.
  • a worldwide research effort, aiming at early detection of ovarian cancer, is currently being performed; finding molecular markers for the disease is one of the major research topics (J Clin Oncol. 2003 May 15;21(10 Suppl):200-5).
  • CA- 125 is a member of the epithelial sialomucins markers group and is the most well documented and the best performing single marker from this group.
  • Another name for CA- 125 is mucin 16, and although it is a membrane protein, it can be found in the serum. Its greatest sensitivity is achieved for serous and endometrioid ovarian tumors compared to mucinous or clear cell tumors.
  • CA-125 is not a marker that can be detected through use of urine samples due to a high molecular weight.
  • CA- 125 There are other ovarian cancer markers originating from epithelial mucins but none can replace CA- 125, due to poorer specificity and sensitivity. These other markers may prove complementary to CA- 125.
  • CA-50, CA 54-61 , C ⁇ -195 and CA 19-9 all appear to have greater sensitivity for detection of mucinous tumors while STN and TAG-72 have better sensitivity for detection of clear cell tumors (Dis Markers. 2004;20(2):53-70).
  • Kallikreins a family of serine proteases, and other protease-related proteins are also potential markers for ovarian cancer. Indeed, the entire family of kallikreins map to a region on chromosome 19q which is shown to be amplified in ovarian cancers. In particular, kallikrein 6 (protease M) and kallilrein 10 have been reported to have sensitivity up to 75% and specificity up to 100%.
  • Matrix metalloproteinases MMPs
  • MMP-2 was reported to have 66% sensitivity and 100% specificity in one study.
  • Cathepsin L a cystein protease
  • Cathepsin L a cystein protease
  • Hormones have a role in normal ovarian physiology. Therefore, it is not surprising that hormones, and growth and inhibition factors as well, are suitable for ovarian cancer detection. Measurements of fragments of gonadotropin in the urine were found to have sensitivity up to 83% and specificity up to 92% for detecting ovarian cancer. Inhibins, members of the Transforming Growth Factors (TGF) beta superfamily, have been shown to have a diagnostic value in the detection of granulosa cell tumor, a relatively uncommon type of ovarian cancer, associated with better prognosis overall.
  • TGF Transforming Growth Factors
  • Serum inhibin is an ovarian product which decreases to non detectable levels after menopause, however, certain ovarian cancers (mucinous carcinomas and sex cord stromal tumours such as granulosa cell tumours) continue to produce inhibin. Studies have shown that that inhibin assays which detect all inhibin forms (as opposed to test detecting specific members of the inhibins family) provide the highest sensitivity/specificity characteristics as an ovarian cancer diagnostic test (MoI Cell Endocrinol. 2002 May 31 ; 191 ( l):97- 103). Measurement of serum TGF-alpha itself was found to have sensitivity up to 70% and specificity of 89% in early stage disease.
  • the growth factor Mesothelin was also found to have diagnostic value but only for late stage disease. lmmunohistochemistry is frequently used to assess the origin of tumor and staging when a pathological tissue sample is available. A few molecular markers have been shown to have diagnostic value in lmmunohistochemistry of ovarian cancer, among them Epidermal Growth Factor, p53 and HER-2. P53 expression is much lower at early stage than late stage disease. P53 high expression is more typical or characteristic of invasive serous tumors than of mucinous tumors. No benign tumors are stained with P53. HER-2 is found in less than 25% of newly diagnosed ovarian cancers.
  • Ovarian cancer of type granulosa cell tumor has in general better prognosis with late relapse and/or metastasis formation. However, about 50% of patients still die within 20 years of diagnosis.
  • immunohistochemistry staining of estrogen receptor beta (ERb) and proliferating cell nuclear antigen (PCNA) showed that loss of ERb expression and high PCNA expression, characterized a subgroup of granulosa cell tumors with a worse outcome (Histopathology. 2003 Sep;43(3):254-62).
  • Survivin expression was also shown to be correlated to tumor grade, histologic type and mutant p53 but actual correlation to survival is questionable (Mod Pathol. 2004 Feb;17(2):264)
  • markers have been tested over the years for ovarian cancer detection. Some markers have shown only limited value while others are still under investigation. Among them are TPA and TPS, two cytokeratins whose inclusion in a panel with CA- 125 resulted in diagnoses with sensitivity up to 93% and specificity up to 98%. LPA - lysophosphatidic acid - was a very promising marker with one study demonstrating 98% sensitivity and 90% specificity. However, this marker is very unstable and requires quick processing and freezing of plasma, and therefore has limited usage.
  • CA- 125 is one of the panel members.
  • the best performing panel combinations so far have been CA- 125 with CA 15-3 with sensitivity of 93% and specificity of 93%, CA- 125 with CEA (which has very little sensitivity by itself) with specificity of 93% and specificity of 93%, and CA- 125 with TAG-72 and CA 15-3 where specificity becomes 95% but sensitivity is diminished (Dis Markers. 2004;20(2):53-70).
  • the background art does not teach or suggest markers for ovarian cancer that are sufficiently sensitive and/or accurate, alone or in combination.
  • the present invention overcomes these deficiencies of the background art by providing novel markers for ovarian cancer that are both sensitive and accurate. These markers are differentially expressed and preferably overexpressed in ovarian cancer specifically, as opposed to normal ovarian tissue.
  • the measurement of these markers, alone or in combination, in patient (biological) samples provides information that the diagnostician can correlate with a probable diagnosis of ovarian cancer.
  • the markers of the present invention alone or in combination, show a high degree of differential detection between ovarian cancer and non-cancerous states.
  • suitable biological samples which may optionally be used with preferred embodiments of the present invention include but are not limited to blood, serum, plasma, blood cells, urine, sputum, saliva, stool, spinal fluid or CSF, lymph fluid, the external secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, milk, neuronal tissue, ovarian tissue, any human organ or tissue, including any tumor or normal tissue, any sample obtained by lavage (for example of the bronchial system or of the female reproductive system), and also samples of in vivo cell culture constituents.
  • the biological sample comprises ovarian tissue and/or a serum sample and/or a urine sample and/or secretions or other samples from the female reproductive system and/or any other tissue or liquid sample.
  • the sample can optionally be diluted with a suitable eluant before contacting the sample to an antibody and/or performing any other diagnostic assay.
  • signalp_hmm refers to Hidden Markov Model
  • nn refers to neural networks. Localization was also determined through manual inspection of known protein localization and/or gene structure, and the use of heuristics by the individual inventor.
  • T - > C means that the SNP results in a change at the position given in the table from T to C.
  • M - > Q means that the SNP has caused a change in the corresponding amino acid sequence, from methionine (M) to glutamine (Q). If, in place of a letter at the right hand side for the nucleotide sequence SNP, there is a space, it indicates that a frameshift has occurred. A frameshift may also be indicated with a hyphen (-). A stop codon is indicated with an asterisk at the right hand side (*).
  • a comment may be found in parentheses after the above description of the SNP itself.
  • This comment may include an FTId, which is an identifier to a SwissProt entry that was created with the indicated SNP.
  • An FTId is a unique and stable feature identifier, which allows construction of links directly from position- specific annotation in the feature table to specialized protein-related databases.
  • the header of the first column is "SNP position(s) on amino acid sequence", representing a position of a known mutation on amino acid sequence.
  • SNPs may optionally be used as diagnostic markers according to the present invention, alone or in combination with one or more other SNPs and/or any other diagnostic marker.
  • Preferred embodiments of the present invention comprise such SNPs, including but not limited to novel SNPs on the known (WT or wild type) protein sequences given below, as well as novel nucleic acid and/or amino acid sequences formed through such SNPs, and/or any SNP on a variant amino acid and/or nucleic acid sequence described herein.
  • P- value including the level of expression in cell- lines (P2)
  • Library-based statistics refer to statistics over an entire library, while EST clone statistics refer to expression only for ESTs from a particular tissue or cancer.
  • microarray results those from microarrays prepared according to a design by the present inventors, for which the microarray fabrication procedure is described in detail in Materials and Experimental Procedures section herein; and those results from microarrays using Affymetrix technology.
  • tissue name was used as the reference to the type of chip for which expression was measured.
  • probe name begins with the name of the cluster (gene), followed by an identifying number.
  • Oligonucleotide microarray results taken from Affymetrix data were from chips available from Affymetrix Inc, Santa Clara, CA, USA (see for example data regarding the
  • the probe names follow the Affymetrix naming convention.
  • NCBI Gene Expression Omnibus see www.ncbi.nlm.nih.gov/projects/geo/ and Edgar et al, Nucleic Acids Research, 2002, Vol. 30, No. 1 207-210).
  • TAA histograms The following list of abbreviations for tissues was used in the TAA histograms.
  • TAA Tumor Associated Antigen
  • TAA histograms represent the cancerous tissue expression pattern as predicted by the biomarkers selection engine, as described in detail in examples 1-5 below (the first word is the abbreviation while the second word is the full name):
  • nucleic acid sequences of the present invention refer to portions of nucleic acid sequences that were shown to have one or more properties as described below. They are also the building blocks that were used to construct complete nucleic acid sequences as described in greater detail below.
  • oligonucleotides which are embodiments of the present invention, for example as amplicons, hybridization units and/or from which primers and/or complementary oligonucleotides may optionally be derived, and/or for any other use.
  • ovarian cancer refers to cancers of the ovary including but not limited to Ovarian epithelial tumors (serous, mucinous, endometroid, clear cell, and Brenner tumor), ovarian germ-cell tumors, (teratoma, dysgerminoma, endodermal sinus tumor, and embryonal carcinoma) and ovarian stromal tumors (originating from granulosa, theca, Sertoli, Leydig, and collagen-producing stromal cells).
  • marker in the context of the present invention refers to a nucleic acid fragment, a peptide, or a polypeptide, which is differentially present in a sample taken from subjects (patients) having ovarian cancer as compared to a comparable sample taken from subjects who do not have ovarian cancer.
  • differentially present refers to differences in the quantity of a marker present in a sample taken from patients having ovarian cancer as compared to a comparable sample taken from patients who do not have ovarian cancer.
  • a nucleic acid fragment may optionally be differentially present between the two samples if the amount of the nucleic acid fragment in one sample is significantly different from the amount of the nucleic acid fragment in the other sample, for example as measured by hybridization and/or NAT-based assays.
  • a polypeptide is differentially present between the two samples if the amount of the polypeptide in one sample is significantly different from the amount of the polypeptide in the other sample. It should be noted that if the marker is detectable in one sample and not detectable in the other, then such a marker can be considered to be differentially present.
  • diagnosis means identifying the presence or nature of a pathologic condition. Diagnostic methods differ in their sensitivity and specificity.
  • the "sensitivity” of a diagnostic assay is the percentage of diseased individuals who test positive (percent of "true positives”). Diseased individuals not detected by the assay are “false negatives.” Subjects who are not diseased and who test negative in the assay are termed “true negatives.”
  • the "specificity” of a diagnostic assay is 1 minus the false positive rate, where the "false positive” rate is defined as the proportion of those without the disease who test positive. While a particular diagnostic method may not provide a definitive diagnosis of a condition, it suffices if the method provides a positive indication that aids in diagnosis.
  • diagnosis refers to classifying a disease or a symptom, determining a severity of the disease, monitoring disease progression, forecasting an outcome of a disease and/or prospects of recovery.
  • detecting may also optionally encompass any of the above.
  • Diagnosis of a disease according to the present invention can be effected by determining a level of a polynucleotide or a polypeptide of the present invention in a biological sample obtained from the subject, wherein the level determined can be correlated with predisposition to, or presence or absence of the disease.
  • a biological sample obtained from the subject may also optionally comprise a sample that has not been physically removed from the subject, as described in greater detail below.
  • the term "level” refers to expression levels of RNA and/or protein or to DNA copy number of a marker of the present invention. Typically the level of the marker in a biological sample obtained from the subject is different (i.e., increased or decreased) from the level of the same variant in a similar sample obtained from a healthy individual (examples of biological samples are described herein).
  • tissue or fluid collection methods can be utilized to collect the biological sample from the subject in order to determine the level of DNA, RNA and/or polypeptide of the variant of interest in the subject.
  • Examples include, but are not limited to, fine needle biopsy, needle biopsy, core needle biopsy and surgical biopsy (e.g., brain biopsy), and lavage. Regardless of the procedure employed, once a biopsy/sample is obtained the level of the variant can be determined and a diagnosis can thus be made. Determining the level of the same variant in normal tissues of the same origin is preferably effected along- side to detect an elevated expression and/or amplification and/or a decreased expression, of the variant as opposed to the normal tissues.
  • test amount of a marker refers to an amount of a marker in a subject's sample that is consistent with a diagnosis of ovarian cancer.
  • a test amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals).
  • a "control amount" of a marker can be any amount or a range of amounts to be compared against a test amount of a marker.
  • a control amount of a marker can be the amount of a marker in a patient with ovarian cancer or a person without ovarian cancer.
  • a control amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals).
  • Detect refers to identifying the presence, absence or amount of the object to be detected.
  • a “label” includes any moiety or item detectable by spectroscopic, photo chemical, biochemical, immunochemical, or chemical means.
  • useful labels include 32 P, 35 S, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin- strep tavadin, dioxigenin, haptens and proteins for which antisera or monoclonal antibodies are available, or nucleic acid molecules with a sequence complementary to a target.
  • the label often generates a measurable signal, such as a radioactive, chromogenic, or fluorescent signal, that can be used to quantify the amount of bound label in a sample.
  • the label can be incorporated in or attached to a primer or probe either covalently, or through ionic, van der Waals or hydrogen bonds, e.g., incorporation of radioactive nucleotides, or biotinylated nucleotides that are recognized by streptavadin.
  • the label may be directly or indirectly detectable. Indirect detection can involve the binding of a second label to the first label, directly or indirectly.
  • the label can be the ligand of a binding partner, such as biotin, which is a binding partner for streptavadin, or a nucleotide sequence, which is the binding partner for a complementary sequence, to which it can specifically hybridize.
  • the binding partner may itself be directly detectable, for example, an antibody may be itself labeled with a fluorescent molecule.
  • the binding partner also may be indirectly detectable, for example, a nucleic acid having a complementary nucleotide sequence can be a part of a branched DNA molecule that is in turn detectable through hybridization with other labeled nucleic acid molecules (see, e.g., P. D. Fahrlander and A. Klausner, Bio/Technology 6:1165 (1988)). Quantitation of the signal is achieved by, e.g., scintillation counting, densitometry, or flow cytometry.
  • Exemplary detectable labels include but are not limited to magnetic beads, fluorescent dyes, radiolabels, enzymes (e.g., horse radish peroxide, alkaline phosphatase and others commonly used in an ELISA), and calorimetric labels such as colloidal gold or colored glass or plastic beads.
  • the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture.
  • immunoassay is an assay that uses an antibody to specifically bind an antigen. The immunoassay is characterized by the use of specific binding properties of a particular antibody to isolate, target, and/or quantify the antigen.
  • the specified antibodies bind to a particular protein at least two times greater than the background (non-specific signal) and do not substantially bind in a significant amount to other proteins present in the sample.
  • Specific binding to an antibody under such conditions may require an antibody that is selected for its specificity for a particular protein.
  • polyclonal antibodies raised to seminal basic protein from specific species such as rat, mouse, or human can be selected to obtain only those polyclonal antibodies that are specifically immunoreactive with seminal basic protein and not with other proteins, except for polymorphic variants and alleles of seminal basic protein.
  • This selection may be achieved by subtracting out antibodies that cross-react with seminal basic protein molecules from other species.
  • a variety of immunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein.
  • solid-phase ELISA immunoassays are routinely used to select antibodies specifically immunoreactive with a protein (see, e.g., Harlow & Lane, Antibodies, A Laboratory Manual (1988), for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity).
  • a specific or selective reaction will be at least twice background signal or noise and more typically more than 10 to 100 times background.
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below amino acid sequence comprising a sequence in the table below
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or
  • nucleic acid sequence compnsing a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or
  • nucleic acid sequence comp ⁇ sing a sequence in the table below.
  • T10888 PEA 1 node 15 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or
  • nucleic acid sequence comp ⁇ sing a sequence in the table below
  • an isolated polypeptide comprising an amino acid sequence in the table below.
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: •4 Transcript Name
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below: Segment Name " -
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • H53393 PEA 1 T9 a nucleic acid sequence comprising a sequence in the table below
  • an isolated polypeptide comprising an amino acid sequence in the table below
  • H53393 PEA 1 P6 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • HSU40434 PEA 1 node 57
  • HSU40434 PEA 1 node 0
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below
  • an isolated polypeptide comprising an amino acid sequence m the table below.
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or
  • nucleic acid sequence comprising a sequence in the table below
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence m the table below and/or
  • nucleic acid sequence comprising a sequence in the table below
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comp ⁇ sing a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • nucleic acid sequence comprising a sequence in the table below
  • an isolated polypeptide comprising an amino acid sequence in the table below: Protein Name
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or
  • nucleic acid sequence comprising a sequence in the table below.
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated chimeric polypeptide encoding for HSMUCl A J ⁇ AJ P63 comprising a first amino acid sequence being at least 90 % homologous to MTPGTQSPFFLLLLLTVLTVVTGSGHASSTPGGEKETSATQRSSV corresponding to amino acids 1 - 45 of MUCl HUMAN, which also corresponds to amino acids 1 - 45 of HSMUC1A PEAJ P63, and a second amino acid sequence being at feast 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK corresponding to amino acids 46 - 85 of HSMUC 1 A PEA 1 P63, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of HSMUC1A PEAJ P63 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK in HSMUC1A_PEA_1_P63.
  • an isolated chimeric polypeptide encoding for T46984 PEA 1 P2 comprising a first amino acid sequence being at least 90 % homologous to
  • FFQLVDVNTGAELTPHQ corresponding to amino acids 1 - 433 of RIB2 HUMAN, which also corresponds to amino acids 1 - 433 of T46984 PEA 1 P3, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ICHIWKLIFLP corresponding to amino acids 434 - 444 of T46984 PEA 1 P3, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for T46984_PEA_l_P10 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of T46984 PEA 1 P10 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homolo gous to the sequence LMDQK in T46984_PEA_l_P10.
  • an isolated chimeric polypeptide encoding for T46984_PEA_1_P11 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for T46984JPEA_1_P12 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of T46984_PEA_1_P12 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SQDLH in T46984_PEA_1_P12.
  • an isolated chimeric polypeptide encoding for T46984 PEA 1 P21 comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence M corresponding to amino acids 1 - I of T46984_PEA_1_P21 , and a second amino acid sequence being at least 90 % homologous to
  • LAILGSVTFLAGNRMLAQQAVKRTAH corresponding to amino acids 70 - 631 of RIB2_HUMAN, which also corresponds to amino acids 2 - 563 of T46984 PEA 1 P21 , wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for T46984_PEA_1_P27 comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHD VERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEG
  • an isolated polypeptide encoding for a tail of T46984_PEA_1_P27 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence FGSGLVPMSPTSLLLLARLYFTWDMLLCWDSCMSTGLSSTCSRP in T46984_PEA_1_P27.
  • an isolated chimeric polypeptide encoding for T46984_PEA_1_P32 comprising a first amino acid sequence being at least 90 % homologous to
  • RYIANTVE corresponding to amino acids 1 - 364 of RIB2 HUMAN, which also corresponds to amino acids 1 - 364 of T46984 PEA 1 P32, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GQVRWLTPVIPALWEAKAGGSPEVRSSILAWPT corresponding to amino acids 365 - 397 of T46984 PEA 1JP32, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of T46984 PEA 1 P32 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GQVRWLTPVIPALWEAKAGGSPEVRSSILAWPT in T46984_PEA_1_P32.
  • an isolated chimeric polypeptide encoding for T46984 PEA 1 P34 comprising a first amino acid sequence being at least 90 % homologous to
  • PLTQATVKLEHAKSVASRATVLQKTSFTPVG corresponding to amino acids 1 - 329 of RIB2 HUMAN, which also corresponds to amino acids 1 - 329 of T46984_PEA_1_P34.
  • an isolated chimeric polypeptide encoding for T46984_PEA_1_P35 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of T46984_PEA_1_P35 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GCWPSRQSREQHISSRRKMEILKTECQEKESRTIHSMRRKMEKKNFI in T46984_PEA_1_P35.
  • an isolated chimeric polypeptide encoding for T46984_PEA_1_P38 comprising a first amino acid sequence being at least 90 % homologpus to
  • an isolated polypeptide encoding for a tail of T46984_PEA_1_P38 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MDPDWCQCLQLHFCS in T46984_PEA_1__P38.
  • an isolated chimeric polypeptide encoding for T46984_PEA_1_P39 comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAA VSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLA corresponding to amino acids 1 - 160 of RIB2 HUMAN, which also corresponds to amino acids 1 - 160 of T46984_PEA_1_P39.
  • an isolated chimeric polypeptide encoding for T46984 PEA 1 P45 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of T46984_PEA_1_P45 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence
  • an isolated chimeric polypeptide encoding for T46984 PEA 1 P46 comprising a first amino acid sequence being at least 90 % homologous to
  • GAQVPDAK corresponding to amino acids 1 - 69 of RIB2 HUMAN, which also corresponds to amino acids 1 - 69 of T46984_PEA_1_P46, and a second amino acid sequence being at least
  • NSPGSADSIPPVPAG corresponding to amino acids 70 - 84 of T46984_PEA_1_P46, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of T46984_PEA_1_P46 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence
  • an isolated chimeric polypeptide encoding for M7853O_PEA_1_P15 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of M78530_PEA_l_P15 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RKSWSSSRPITSMFLSPGSPEPASANTARS in M78530_PEA_l_P15.
  • an isolated chimeric polypeptide encoding for M78530_PEA_l_P15 comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MRLSPAPLKLSRTPALLALALPLAAALAFSDETLDKVPKSEGYCSRILRAQGTRREGYT EFSLRVEGDPDFYKPGTSYRVTLS corresponding to amino acids 1 - 83 of M78530_PEA_l_P15, a second amino acid sequence being at least 90 % homologous to AAPPSYFRGFTLIALRENREGDKEEDHAGTFQIIDEEETQFMSNCPVA VTESTPRRRTRIQ VFWIAPPAGTGCVILKASIVQKRIIYFQDEGSLTKKLCEQDSTFDGVTDKPILDCCACGT AKYRLTFYGNWSEKTHPKDY
  • an isolated polypeptide encoding for a head of M78530 PEA 1 P15 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MRLSPAPLKLSRTPALLALALPLAAALAFSDETLDKVPKSEGYCSRILRAQGTRREGYT EFSLRVEGDPDFYKPGTSYRVTLS of M78530_PEA_l_P15.
  • An isolated polypeptide encoding for a tail of M78530_PEA_l_P15 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RKSWSSSRPITSMFLSPGSPEPASANTARS in M78530_PEA_l_P15.
  • an isolated chimeric polypeptide encoding for M78530_PEA_l_P16 comprising a first amino acid sequence being at least 90 % homologous to MRLSPAPLKLSRTPALLALALPLAAALAFSDETLDKVPKSEGYCSRILRAQGTRREGYT EFSLRVEGDPDFYKPGTSYRVTLSAAPPSYFRGFTLIALRENREGDKEEDHAGTFQIIDEE ETQFMSNCPVA VTESTPRRRTRIQVFWIAPPAGTGCVILKASIVQKRIIYFQDEGSLTKKL CEQDSTFDGVTDKPILDCCACGTAKYRLTFYGNWSEKTHPKDYPRRANHWSAIIGGSH SKNYVLWEYGGYASEGVKQVAELGSPVKMEEEIRQQSDEVLTVIKAKAQWPAWQPLN
  • V corresponding to amino acids 1 - 297 of Q8NCD7, which also corresponds to amino acids 1 - 297 of M78530_PEA_l_P16.
  • an isolated chimeric polypeptide encoding for M78530_PEA_l_P16 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for M78530_PEA_l_P16 comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MRLSPAPLKLSRTPALLALALPLAAALAFSDETLDKVPKSEGYCSRILRAQGTRREGYT EFSLRVEGDPDFYKPGTSYRVTLS corresponding to amino acids 1 - 83 of
  • M78530_PEA_l_P16 and a second amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a head of M78530_PEA_l_P16 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MRLSPAPLKLSRTPALLALALPLAAALAFSDETLDKVPKSEGYCSRILRAQGTRREGYT EFSLRVEGDPDFYKPGTSYRVTLS of M78530_PEA_1_P 16.
  • an isolated chimeric polypeptide encoding for M7853O_PEA_1_P17 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of M78530_PEA_l_P17 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRQKNHRMTK in M78530_PEA_l_P17.
  • an isolated chimeric polypeptide encoding for M78530_PEA_l_P17 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of M78530_PEA_l_P17 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRQKNHRMTK in M78530 PEA 1 P17.
  • an isolated chimeric polypeptide encoding for M78530_PEA_l_P17 comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MRLSPAPLKLSRTPALLALALPLAAALAFSDETLDKVPKSEGYCSRJLRAQGTRREGYT EFSLRVEGDPDFYKPGTSYRVTLS corresponding to amino acids 1 - 83 of M78530_PEA_l_P17, a second amino acid sequence being at least 90 % homologous to AAPPSYFRGFTLIALRENREGDKEEDHAGTFQIIDEEETQFMSNCPVA VTESTPRRRTRIQ VFWIAPPAGTGCVILKASIVQKRIIYFQDEGSLTKKLCEQDSTFDGVTDKPILDCCACGT AKYRLTFYGNWSEKTHPK
  • an isolated polypeptide encoding for a headofM78530_PEA_l_P17 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MRLSPAPLKLSRTPALLALALPLAAALAFSDETLDKVPKSEGYCSRJLRAQGTRREGYTEFSLR
  • an isolated polypeptide encoding for a tail of M78530_PEA_l_P17 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRQKNHRMTK in M78530_PEA_l_P17.
  • an isolated chimeric polypeptide encoding for T48119_P2 comprising a first amino acid sequence being at least 90 % homologous to MTRQMASSGASGGKIDNSVL VLIVGLSTVGAGA YA YKTMKEDEKRYNERJSGLGLTPE
  • VLWNIFNRMPIARKIIKDGEQHEDLNEVAKLFNIHED corresponding to amino acids 50 - 613 of PCD8_HUMAN, which also corresponds to amino acids 1 - 564 of T481 19JP2.
  • an isolated chimeric polypeptide encoding for T48119_P2 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for T39971_P6, comprising a first amino acid sequence being at least 90 % homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAP APEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFD AFTDLKNGSLFAFR GQYCYELDEKA VRPGYPKLIRD VWGIEGPID AAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKG corresponding to amino acids 1 - 276 of VTNC H UMAN, which also corresponds to amino acids 1 - 276 of T39971 P6, and a second amino acid sequence being at
  • an isolated chimeric polypeptide encoding for T39971_P9 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for an edge portion of T39971_P9 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise TS, having a structure as follows: a sequence starting from any of amino acid numbers 325-x to 325; and ending at any of amino acid numbers 326 + ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for an edge portion of T39971_P 1 1 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327 + ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for T39971_P 1 1 comprising a first amino acid sequence being at least 90 % homologous to
  • CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids 1 - 326 of Q9BSH7, which also corresponds to amino acids 1 - 326 of T39971 P11, and a second amino acid sequence being at least 90 % homologous to
  • DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442 - 478 of Q9BSH7, which also corresponds to amino acids 327 - 363 of T39971 P11, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for an edge portion of T39971 P11 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327 + ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for T39971 P12 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of T39971_P12 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV in T39971_P12.
  • an isolated chimeric polypeptide encoding for T39971_P12 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of T39971 P12 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV in T39971 P12.
  • an isolated chimeric polypeptide encoding for Z44808_PEA_l_P5 comprising a first amino acid sequence being at least 90 % homologous to MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGR TFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDD GTYSQVQCHSYTGYCWCVTPNGRPISGTA VAHKTPRCPGSVNEKLPQREGTGKTDDAA APALETQPQGDEEDIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKN DNWIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPA KARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGR
  • an isolated polypeptide encoding for a tail of Z44808_PEA_l_P5 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DAMVVSSRPKATTHRKSRTLSRR in Z44808_PEA_l_P5.
  • an isolated chimeric polypeptide encoding for Z44808 PEA 1 P7 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of Z44808_PEA_l_P7 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLWLRGKVSFYCF in Z44808 PEA 1 P7.
  • an isolated chimeric polypeptide encoding for an edge portion of Z44808 PEA 1 P11 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise TD, having a structure as follows: a sequence starting from any of amino acid numbers 170-x to - 170; and ending at any of amino acid numbers 171+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for S67314_PEA_1_P4 comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1 - 116 of FABH_HUMAN, which also corresponds to amino acids 1 - 1 16 of S67314 PEA 1 P4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRWATLELY
  • an isolated polypeptide encoding for a tail of S67314 PEA 1 P4 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence
  • an isolated polypeptide encoding for a tail of S67314_PEA_1_P4 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRWATLELYLIGYYYCSFSQACSKKPSPPLRA VEAGTREWLWVRVVSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGINNTNL VGLLGSL in S67314 PEAJ P4.
  • an isolated chimeric polypeptide encoding for S67314_PEA_1_P5 comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1 - 116 of FABH HUM AN, which also corresponds to amino acids 1 - 1 16 of S67314_PEA_1_P5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence
  • an isolated chimeric polypeptide encoding for S67314_PEA_1_P5 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of S67314_PEA_1_P5 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG KSIV in S67314_PEA_1_P5.
  • an isolated chimeric polypeptide encoding for S67314 PEA 1 P6, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1 - 116 of FABH HUMAN, which also corresponds to amino acids 1 - 116 of S67314 PEA 1 P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MEKLQLRNVK
  • an isolated polypeptide encoding for a tail of S67314_PEA_1_P6 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MEKLQLRNVK in S67314_PEA_1_P6.
  • an isolated chimeric polypeptide encoding for S67314 PEA 1 P7 comprising a first amino acid sequence being at least 90 % homologous to MVD AFLGTWKLVDSKNFDD YMKSL corresponding to amino acids 1 - 24 of FABH_HUMAN, which also corresponds to amino acids 1 - 24 of S67314_PEA_1_P7, second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AHILITFPLPS corresponding to amino acids 25 - 35 of S67314 PEA 1 P7, and a third amino acid sequence being at least 90 % homologous to

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Abstract

La présente invention se rapporte à de nouveaux marqueurs du cancer de l'ovaire, qui sont à la fois sensibles et précis. Les marqueurs selon l'invention font l'objet d'une surexpression et/ou d'une expression différentielle en cas de cancer de l'ovaire, en particulier, par rapport à un tissu ovarien normal. La mesure desdits marqueurs, seuls ou combinés, dans des échantillons prélevés sur des patients, livre des informations que le diagnosticien peut mettre en corrélation avec un diagnostic probable de cancer de l'ovaire. Les marqueurs selon l'invention, seuls ou combinés, permettent d'atteindre un degré élevé de détection différentielle entre un cancer de l'ovaire et un état non cancéreux.
PCT/IB2005/002555 2004-01-27 2005-01-27 Expression differentielle de marqueurs dans le cancer de l'ovaire WO2005116850A2 (fr)

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AU2005248530A AU2005248530A1 (en) 2004-01-27 2005-01-27 Differential expression of markers in ovarian cancer
EP05780004A EP1721257A2 (fr) 2004-01-27 2005-01-27 Expression differentielle de marqueurs dans le cancer de l'ovaire
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US11/043,806 US7368548B2 (en) 2004-01-27 2005-01-27 Nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of prostate cancer
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