JP5878904B2 - 腫瘍の同定 - Google Patents
腫瘍の同定 Download PDFInfo
- Publication number
- JP5878904B2 JP5878904B2 JP2013209489A JP2013209489A JP5878904B2 JP 5878904 B2 JP5878904 B2 JP 5878904B2 JP 2013209489 A JP2013209489 A JP 2013209489A JP 2013209489 A JP2013209489 A JP 2013209489A JP 5878904 B2 JP5878904 B2 JP 5878904B2
- Authority
- JP
- Japan
- Prior art keywords
- genes
- tumor
- gene
- expression
- sequences
- 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.)
- Active
Links
- 206010028980 Neoplasm Diseases 0.000 title claims description 274
- 230000014509 gene expression Effects 0.000 claims description 213
- 210000004027 cell Anatomy 0.000 claims description 121
- 238000000034 method Methods 0.000 claims description 112
- 210000004881 tumor cell Anatomy 0.000 claims description 29
- 241000282414 Homo sapiens Species 0.000 claims description 22
- 238000002493 microarray Methods 0.000 claims description 12
- 238000004422 calculation algorithm Methods 0.000 claims description 7
- 238000007635 classification algorithm Methods 0.000 claims description 7
- 108090000623 proteins and genes Proteins 0.000 description 444
- 239000000523 sample Substances 0.000 description 137
- 210000001519 tissue Anatomy 0.000 description 49
- 108091033319 polynucleotide Proteins 0.000 description 45
- 102000040430 polynucleotide Human genes 0.000 description 45
- 239000002157 polynucleotide Substances 0.000 description 45
- 201000011510 cancer Diseases 0.000 description 36
- 150000007523 nucleic acids Chemical class 0.000 description 28
- 102000039446 nucleic acids Human genes 0.000 description 27
- 108020004707 nucleic acids Proteins 0.000 description 27
- 238000001514 detection method Methods 0.000 description 25
- 238000003753 real-time PCR Methods 0.000 description 24
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 20
- 230000000875 corresponding effect Effects 0.000 description 16
- 125000003729 nucleotide group Chemical group 0.000 description 16
- 238000009396 hybridization Methods 0.000 description 15
- 239000002773 nucleotide Substances 0.000 description 15
- 108091026890 Coding region Proteins 0.000 description 14
- 238000003556 assay Methods 0.000 description 14
- 230000036541 health Effects 0.000 description 14
- 238000005259 measurement Methods 0.000 description 12
- 210000004185 liver Anatomy 0.000 description 10
- 210000000056 organ Anatomy 0.000 description 10
- 230000000295 complement effect Effects 0.000 description 9
- 230000002596 correlated effect Effects 0.000 description 9
- 108020004999 messenger RNA Proteins 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 238000003752 polymerase chain reaction Methods 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 238000012549 training Methods 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 230000035897 transcription Effects 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 206010025323 Lymphomas Diseases 0.000 description 7
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 7
- 206010039491 Sarcoma Diseases 0.000 description 7
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 7
- 230000003321 amplification Effects 0.000 description 7
- 238000004891 communication Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 210000004602 germ cell Anatomy 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 238000003199 nucleic acid amplification method Methods 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 101150113019 74 gene Proteins 0.000 description 6
- 201000009030 Carcinoma Diseases 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000000481 breast Anatomy 0.000 description 6
- 238000012790 confirmation Methods 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 6
- 238000003757 reverse transcription PCR Methods 0.000 description 6
- 210000003932 urinary bladder Anatomy 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- 208000018142 Leiomyosarcoma Diseases 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 210000002429 large intestine Anatomy 0.000 description 5
- 238000012423 maintenance Methods 0.000 description 5
- 206010027191 meningioma Diseases 0.000 description 5
- 201000008968 osteosarcoma Diseases 0.000 description 5
- 230000002611 ovarian Effects 0.000 description 5
- 210000000496 pancreas Anatomy 0.000 description 5
- 102000054765 polymorphisms of proteins Human genes 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 238000004393 prognosis Methods 0.000 description 5
- 210000002307 prostate Anatomy 0.000 description 5
- 210000000813 small intestine Anatomy 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 206010027406 Mesothelioma Diseases 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000002790 cross-validation Methods 0.000 description 4
- 210000000981 epithelium Anatomy 0.000 description 4
- 239000012520 frozen sample Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 210000000232 gallbladder Anatomy 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- 206010024627 liposarcoma Diseases 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000008488 polyadenylation Effects 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 210000004872 soft tissue Anatomy 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 101150052384 50 gene Proteins 0.000 description 3
- 101150079187 87 gene Proteins 0.000 description 3
- 206010001197 Adenocarcinoma of the cervix Diseases 0.000 description 3
- 208000034246 Adenocarcinoma of the cervix uteri Diseases 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 3
- 241000945470 Arcturus Species 0.000 description 3
- 208000003950 B-cell lymphoma Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 108091092724 Noncoding DNA Proteins 0.000 description 3
- 201000010208 Seminoma Diseases 0.000 description 3
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 3
- 208000009956 adenocarcinoma Diseases 0.000 description 3
- 230000001919 adrenal effect Effects 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 201000006662 cervical adenocarcinoma Diseases 0.000 description 3
- 208000006990 cholangiocarcinoma Diseases 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 210000004696 endometrium Anatomy 0.000 description 3
- 239000000834 fixative Substances 0.000 description 3
- 201000006585 gastric adenocarcinoma Diseases 0.000 description 3
- 238000000370 laser capture micro-dissection Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 201000008806 mesenchymal cell neoplasm Diseases 0.000 description 3
- 238000001668 nucleic acid synthesis Methods 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- -1 phospho Chemical class 0.000 description 3
- 230000002797 proteolythic effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000001685 thyroid gland Anatomy 0.000 description 3
- 101150008989 55 gene Proteins 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 208000006168 Ewing Sarcoma Diseases 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108010026552 Proteome Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 206010042971 T-cell lymphoma Diseases 0.000 description 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 210000004100 adrenal gland Anatomy 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 238000013528 artificial neural network Methods 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 210000003679 cervix uteri Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 208000030381 cutaneous melanoma Diseases 0.000 description 2
- 230000002380 cytological effect Effects 0.000 description 2
- 208000023965 endometrium neoplasm Diseases 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000001001 laser micro-dissection Methods 0.000 description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 230000011278 mitosis Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 201000003708 skin melanoma Diseases 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000012706 support-vector machine Methods 0.000 description 2
- 230000002381 testicular Effects 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 101150029429 38 gene Proteins 0.000 description 1
- 101150021183 65 gene Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 208000036764 Adenocarcinoma of the esophagus Diseases 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000029862 Barrett adenocarcinoma Diseases 0.000 description 1
- 208000023514 Barrett esophagus Diseases 0.000 description 1
- 208000023665 Barrett oesophagus Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 208000032320 Germ cell tumor of testis Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 206010023856 Laryngeal squamous cell carcinoma Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010052399 Neuroendocrine tumour Diseases 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 206010030137 Oesophageal adenocarcinoma Diseases 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 1
- 208000036765 Squamous cell carcinoma of the esophagus Diseases 0.000 description 1
- 208000036844 Squamous cell carcinoma of the larynx Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000033133 Testicular seminomatous germ cell tumor Diseases 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 208000010097 Unknown Primary Neoplasms Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 101150010487 are gene Proteins 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- 210000000270 basal cell Anatomy 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 201000003714 breast lobular carcinoma Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000003936 denaturing gel electrophoresis Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 201000011025 embryonal testis carcinoma Diseases 0.000 description 1
- 201000003914 endometrial carcinoma Diseases 0.000 description 1
- 208000010932 epithelial neoplasm Diseases 0.000 description 1
- 208000028653 esophageal adenocarcinoma Diseases 0.000 description 1
- 208000007276 esophageal squamous cell carcinoma Diseases 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 201000008396 gallbladder adenocarcinoma Diseases 0.000 description 1
- 238000011223 gene expression profiling Methods 0.000 description 1
- 208000026436 grade III glioma Diseases 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000009546 lung large cell carcinoma Diseases 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 238000001531 micro-dissection Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000022669 mucinous neoplasm Diseases 0.000 description 1
- 238000013188 needle biopsy Methods 0.000 description 1
- 208000025402 neoplasm of esophagus Diseases 0.000 description 1
- 208000016065 neuroendocrine neoplasm Diseases 0.000 description 1
- 201000011519 neuroendocrine tumor Diseases 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 210000004882 non-tumor cell Anatomy 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 208000013371 ovarian adenocarcinoma Diseases 0.000 description 1
- 208000021284 ovarian germ cell tumor Diseases 0.000 description 1
- 201000007428 ovarian mucinous adenocarcinoma Diseases 0.000 description 1
- 208000012988 ovarian serous adenocarcinoma Diseases 0.000 description 1
- 208000016517 ovarian serous tumor Diseases 0.000 description 1
- 201000006588 ovary adenocarcinoma Diseases 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 208000011581 secondary neoplasm Diseases 0.000 description 1
- 210000003728 serous cell Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 208000020352 skin basal cell carcinoma Diseases 0.000 description 1
- 201000010106 skin squamous cell carcinoma Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 208000017572 squamous cell neoplasm Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 206010062123 testicular embryonal carcinoma Diseases 0.000 description 1
- 208000002918 testicular germ cell tumor Diseases 0.000 description 1
- 208000024662 testicular seminoma Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
Images
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
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
- G16B25/10—Gene or protein expression profiling; Expression-ratio estimation or normalisation
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
- G16B40/10—Signal processing, e.g. from mass spectrometry [MS] or from PCR
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
- G16B40/20—Supervised data analysis
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
- G16B40/30—Unsupervised data analysis
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
- G16H20/10—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
- G16H50/20—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
-
- 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
- C12Q1/6813—Hybridisation assays
- C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
- C12Q1/6837—Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
-
- 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
-
- 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
- C12Q2600/158—Expression markers
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Chemical & Material Sciences (AREA)
- Medical Informatics (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Theoretical Computer Science (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Computational Biology (AREA)
- Evolutionary Biology (AREA)
- Data Mining & Analysis (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- Databases & Information Systems (AREA)
- Software Systems (AREA)
- Evolutionary Computation (AREA)
- Artificial Intelligence (AREA)
- Bioethics (AREA)
- Computer Vision & Pattern Recognition (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Primary Health Care (AREA)
- Signal Processing (AREA)
- Medicinal Chemistry (AREA)
Description
本発明は、ヒト腫瘍を分類するための遺伝子発現の使用に関する。分類は、ある種の組織から生じる腫瘍と相関し、ならびにある種の腫瘍型と相関する50またはそれより多い発現配列の遺伝子発現プロフィールまたはパターンの使用により実施される。本発明は、その発現が種々の癌における組織源および腫瘍型と相関する50またはそれより多い特定遺伝子配列の使用も提供する。遺伝子発現プロフィールは、核酸発現、タンパク質発現または他の発現フォーマットのいずれにおいて具体化されようと、組織型のまたは組織起源からの腫瘍細胞を含有するとして細胞含有試料を確定して、癌のより精確な同定を、したがってその治療をならびに試料が得られた被験者の予後を可能にするために用いられ得る。
本発明は、臨床設定において被験者から得られる細胞含有試料中の、例えばホルマリン固定、パラフィン包埋(FFPE)試料の場合の、腫瘍を分類するかまたは同定するための遺伝子発現測定の使用に関する。本発明は、臨床的FFPE試料に関する試験を実行しなければならない病院およびその他の実験室が直面する現実世界の条件において腫瘍を分類する能力を提供する。本発明は、他の試料、例えば処理を全く乃至ほとんど受けないかまたは最低限の処理を受けた生鮮試料(例えば単に低い非凍結温度で保存)、ならびに凍結試料にも適用され得る。試料は、原発性腫瘍試料のものであるか、あるいは別の腫瘍の転移に起因した腫瘍のものであり得る。あるいは試料は、細胞学的試料、例えば血液試料中の血球であり得るが、これらに限定されない。一腫瘍試料のいくつかの場合、腫瘍は伝統的病理学的技法による分類を受けていないことはなく、最初に分類されたがしかし確証が所望され、あるいは「未知の原発性の癌腫」(CUP)または「未知の起源の腫瘍」(TUO)または「未知の原発性腫瘍」として分類されている。確証の必要性は、標準技法を用いた5〜10%の分類の間違いにかんがみて、特に当を得ている。したがって本発明は、癌同定またはCIDのための手段を提供すると考えられ得る。
本発明は、慣用的病理学技法を用いて可能であるより客観的なやり方で腫瘍を分類するための遺伝子発現情報の使用方法を提供する。本発明は、一部は、複数の腫瘍型、例えば下記のおよび米国特許仮出願60/577,084号(2004年6月4日発行)に記載された34腫瘍型のうちの1つとして腫瘍試料を分類するために用いられる遺伝子配列の数の無作為低減の結果に基づいている。用いられる試料中で低または一定シグナルを表示する遺伝子の除去に基づいたより大きな組から濾し落とされた総数16,948の遺伝子が、以下の実施例に記載されるような交差妥当化および予測精度の療法のために用いられた。全体からの、50、100、150、200、250、300、400、500、600、700、800、900、1000、1200、1400、1600、1800、2000、2200、2400、2600、2800、3000およびそれより多い遺伝子の100無作為選択が選択され、そして本明細書中に記載されるような分類のために用いられた。
以下の表は、実施例2に用いられる既知の腫瘍の試料の型および数を示す。
100試料からの精度の平均および95%信頼区間を算定し、50〜16948遺伝子を各ステップに関してプロットした。プロットは、KNN(k‐最近傍)アルゴリズムからの交差妥当化および予測精度対偶然選択された遺伝子の数を示した。無作為遺伝子選択は、Rソフトウエアにおける無作為サンプリング関数を用いた。
39腫瘍型間を分類するために用いられる100無作為選択発現遺伝子配列のサブセットを、39腫瘍型のサブセット間を分類するそれらの能力に関して試験した。100発現配列の50、55、60、65、70、75、80、85、90、95および100すべての無作為組合せ(各組合せを10回サンプリング)の発現レベルを、腫瘍型からのデータとともに用い、次に2〜39すべての型の範囲の腫瘍試料(各々10回サンプリングした)の試験無作為組を予測した。図1は、種々の遺伝子組の分類能力が分類された腫瘍型の数と比較して示される、ということを示す。予測どおり、遺伝子配列の数が多いほど、腫瘍型を分類するために要する精度は高い。図2は、用いられる遺伝子配列の数と比較した腫瘍型の種々の数に関する分類実施を示す。
74遺伝子の第一組みおよび90遺伝子の第二組(2つの組は38成員を共通して有する)を、本発明の実行に用いた。2つの組対腫瘍型数の変化の性能を、図3に示す。
上記のように、PCR、例えば定量的PCRの使用により、遺伝子発現の確定または測定を実施し得る。ヒトゲノム中の50またはそれより多い発現配列の発現の検出は、本発明のこのような実施形態に用いられ得る。さらに、74の組、90の組または2つの組合せ組(2つの組の間で共通の38遺伝子配列の存在が存在するとすれば、合計126の遺伝子配列を有する)中の50またはそれより多い遺伝子配列の発現レベルも用いられ得る。本発明は、そのすべてが74の組または90の組のいずれかに存在する87遺伝子配列(あるいはその50またはそれより多い配列)の、上記のような、発現レベルを測定するための定量的PCRの使用を意図する。87遺伝子配列のうち、60は74の組中に存在し、そして63は90の組中に存在する。87遺伝子配列の識別名/寄託番号は、AA456140、AA745593、AA765597、AA782845、AA865917、AA946776、AA993639、AB038160、AF104032、AF133587、AF301598、AF332224、AI041545、AI147926、AI309080、AI341378、AI457360、AI620495、AI632869、AI683181、AI685931、AI802118、AI804745、AI952953、AI985118、AJ000388、AK025181、AK027147、AK054605、AL023657、AL039118、AL110274、AL157475、AW118445、AW194680、AW291189、AW298545、AW445220、AW473119、AY033998、BC000045、BC001293、BC001504、BC001639、BC002551、BC004331、BC004453、BC005364、BC006537、BC006811、BC006819、BC008764、BC008765、BC009084、BC009237、BC010626、BC011949、BC012926、BC013117、BC015754、BC017586、BE552004、BE962007、BF224381、BF437393、BF446419、BF592799、BI493248、H05388、H07885、H09748、M95585、N64339、NM_000065、NM_001337、NM_003914、NM_004062、NM_004063、NM_004496、NM_006115、NM_019894、NM_033229、R15881、R45389、R61469、X69699およびX96757である。
Claims (4)
- 一組織型の腫瘍細胞を含有するものとして細胞含有試料を分類する方法であって、以下の:
ヒト被験者から得られた腫瘍細胞含有試料中の細胞から50またはそれより多い転写配列に対応するRNA分子の発現レベルを確定し;
距離ベースの分類アルゴリズムを用いて、前記50またはそれより多い転写配列の発現レベルを、2以上の既知の腫瘍型のうち複数の腫瘍型における同一の50またはそれより多い転写配列の発現レベルと比較し;そして
前記配列の発現レベルに基づいて、最も類似する発現パターンを有する腫瘍試料を同定し、前記複数の腫瘍型から1つの腫瘍の腫瘍細胞を含有するものとして試料を分類すること;
を包含する方法。 - 前記発現レベルがマイクロアレイの使用により確定される請求項1記載の方法。
- 前記分類が60%またはそれより高い精度を有する請求項1または2記載の方法。
- 前記距離ベースの分類アルゴリズムがk‐最近傍アルゴリズムである請求項1ないし3のいずれか1項に記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US57708404P | 2004-06-04 | 2004-06-04 | |
US60/577,084 | 2004-06-04 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007515665A Division JP5690039B2 (ja) | 2004-06-04 | 2005-06-03 | 腫瘍の同定 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2014183838A JP2014183838A (ja) | 2014-10-02 |
JP5878904B2 true JP5878904B2 (ja) | 2016-03-08 |
Family
ID=35463477
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007515665A Active JP5690039B2 (ja) | 2004-06-04 | 2005-06-03 | 腫瘍の同定 |
JP2013209489A Active JP5878904B2 (ja) | 2004-06-04 | 2013-10-04 | 腫瘍の同定 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007515665A Active JP5690039B2 (ja) | 2004-06-04 | 2005-06-03 | 腫瘍の同定 |
Country Status (12)
Country | Link |
---|---|
US (4) | US20060094035A1 (ja) |
EP (2) | EP2371969B1 (ja) |
JP (2) | JP5690039B2 (ja) |
KR (1) | KR20070057761A (ja) |
CN (1) | CN101035909A (ja) |
AU (1) | AU2005250495A1 (ja) |
CA (1) | CA2569531A1 (ja) |
DK (1) | DK1751313T3 (ja) |
ES (2) | ES2682466T3 (ja) |
IL (1) | IL179811A (ja) |
MX (1) | MXPA06014116A (ja) |
WO (1) | WO2005118879A2 (ja) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040219565A1 (en) | 2002-10-21 | 2004-11-04 | Sakari Kauppinen | Oligonucleotides useful for detecting and analyzing nucleic acids of interest |
US20120258442A1 (en) | 2011-04-09 | 2012-10-11 | bio Theranostics, Inc. | Determining tumor origin |
AU2005250495A1 (en) | 2004-06-04 | 2005-12-15 | Aviaradx, Inc. | Identification of tumors |
EP1838870A2 (en) * | 2004-12-29 | 2007-10-03 | Exiqon A/S | NOVEL OLIGONUCLEOTIDE COMPOSITIONS AND PROBE SEQUENCES USEFUL FOR DETECTION AND ANALYSIS OF MICRORNAS AND THEIR TARGET MRNAs |
US20070065840A1 (en) * | 2005-03-23 | 2007-03-22 | Irena Naguibneva | Novel oligonucleotide compositions and probe sequences useful for detection and analysis of microRNAS and their target mRNAS |
US20060286579A1 (en) * | 2005-06-03 | 2006-12-21 | Aviaradx, Inc. | Normalization genes |
EP2365092A1 (en) * | 2005-06-03 | 2011-09-14 | Aviaradx, Inc. | Identification of tumors and tissues |
WO2007073737A1 (en) * | 2005-12-29 | 2007-07-05 | Exiqon A/S | Detection of tissue origin of cancer |
JP2007267692A (ja) * | 2006-03-31 | 2007-10-18 | Sysmex Corp | 乳がんのリンパ節転移マーカー、プライマ及びこのマーカーを用いた乳がんのリンパ節転移判定方法 |
US20100113284A1 (en) * | 2008-04-04 | 2010-05-06 | Alexander Aristarkhov | Small interfering rna (sirna) target site blocking oligos and uses thereof |
EP2419533A4 (en) * | 2009-04-16 | 2014-12-31 | Nat Res Council Canada | METHOD FOR DETECTING TUMOR CHARACTER STIKA AND MARKER SETS, TUMOR CLASSIFICATION AND MARKER SETS FOR CANCER |
JP2014518086A (ja) * | 2011-06-29 | 2014-07-28 | バイオセラノスティクス インコーポレイテッド | 腫瘍起源の決定 |
WO2014160645A2 (en) | 2013-03-15 | 2014-10-02 | Biotheranostics, Inc. | Neuroendocrine tumors |
CN109055562B (zh) * | 2018-10-29 | 2022-12-20 | 深圳市颐康生物科技有限公司 | 一种生物标志物、预测肾细胞癌的复发和死亡风险的方法 |
EP3938536A4 (en) * | 2019-03-12 | 2023-03-08 | Crown Bioscience (Suzhou) Inc. | METHODS AND COMPOSITIONS FOR IDENTIFICATION OF TUMOR MODELS |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6285701B1 (en) | 1998-08-06 | 2001-09-04 | Lambda Physik Ag | Laser resonator for improving narrow band emission of an excimer laser |
AU1820100A (en) | 1998-11-13 | 2000-06-05 | Pro Duct Health, Inc. | Devices and methods to identify ductal orifices during nipple aspiration |
US6647341B1 (en) | 1999-04-09 | 2003-11-11 | Whitehead Institute For Biomedical Research | Methods for classifying samples and ascertaining previously unknown classes |
AU2001264559A1 (en) * | 2000-06-05 | 2001-12-17 | Avalon Pharmaceuticals | Cancer gene determination and therapeutic screening using signature gene sets |
EP1339872A2 (en) * | 2000-09-19 | 2003-09-03 | Whitehead Institute For Biomedical Research | Genetic markers for tumors |
JP4222835B2 (ja) | 2001-03-14 | 2009-02-12 | 株式会社Dnaチップ研究所 | 癌の予測方法 |
AU2002306768A1 (en) * | 2001-03-20 | 2002-10-03 | Ortho-Clinical Diagnostics, Inc. | Expression profiles and methods of use |
WO2002101357A2 (en) | 2001-06-10 | 2002-12-19 | Irm Llc | Molecular signatures of commonly fatal carcinomas |
AU2002316251A1 (en) * | 2001-06-18 | 2003-01-02 | Rosetta Inpharmatics, Inc. | Diagnosis and prognosis of breast cancer patients |
US7504222B2 (en) * | 2001-10-31 | 2009-03-17 | Millennium Pharmaceuticals, Inc. | Compositions, kits, and methods for identification, assessment, prevention, and therapy of breast cancer |
US20030225526A1 (en) | 2001-11-14 | 2003-12-04 | Golub Todd R. | Molecular cancer diagnosis using tumor gene expression signature |
US20040002067A1 (en) * | 2001-12-21 | 2004-01-01 | Erlander Mark G. | Breast cancer progression signatures |
EP2241636A1 (en) * | 2002-03-13 | 2010-10-20 | Genomic Health, Inc. | Gene expression profiling in biopsied tumor tissues |
US20040098367A1 (en) | 2002-08-06 | 2004-05-20 | Whitehead Institute For Biomedical Research | Across platform and multiple dataset molecular classification |
WO2004048938A2 (en) * | 2002-11-26 | 2004-06-10 | Protein Design Labs, Inc. | Methods of detecting soft tissue sarcoma, compositions and methods of screening for soft tissue sarcoma modulators |
WO2004079014A2 (en) * | 2003-03-04 | 2004-09-16 | Arcturus Bioscience, Inc. | Signatures of er status in breast cancer |
US20060265138A1 (en) | 2003-03-14 | 2006-11-23 | David Bowtell | Expression profiling of tumours |
US20050003341A1 (en) * | 2003-07-01 | 2005-01-06 | Hanan Polansky | Drug discovery assays based on the biology of atherosclerosis, cancer, and alopecia |
EP1709152A4 (en) | 2003-12-15 | 2007-11-07 | Univ California | MOLECULAR SIGNATURE OF PTEN TUMOR SUPPRESSOR |
WO2005068664A2 (en) | 2004-01-09 | 2005-07-28 | The Regents Of The University Of California | Cell-type-specific patterns of gene expression |
US20050272061A1 (en) | 2004-02-19 | 2005-12-08 | Seattle Genetics, Inc. | Expression profiling in non-small cell lung cancer |
AU2005250495A1 (en) | 2004-06-04 | 2005-12-15 | Aviaradx, Inc. | Identification of tumors |
JP2008528024A (ja) | 2005-01-31 | 2008-07-31 | ディジタルジェノミクスインコーポレーション | 肺癌診断用マーカー遺伝子 |
EP2365092A1 (en) * | 2005-06-03 | 2011-09-14 | Aviaradx, Inc. | Identification of tumors and tissues |
WO2007137366A1 (en) | 2006-05-31 | 2007-12-06 | Telethon Institute For Child Health Research | Diagnostic and prognostic indicators of cancer |
WO2008116592A1 (en) | 2007-03-23 | 2008-10-02 | F. Hoffmann-La Roche Ag | Apex as a marker for lung cancer |
US20100273172A1 (en) | 2007-03-27 | 2010-10-28 | Rosetta Genomics Ltd. | Micrornas expression signature for determination of tumors origin |
CA2678919A1 (en) | 2007-03-27 | 2008-10-02 | Ranit Aharonov | Gene expression signature for classification of cancers |
US9133522B2 (en) | 2007-10-31 | 2015-09-15 | Rosetta Genomics Ltd. | Compositions and methods for the diagnosis and prognosis of mesothelioma |
US20110077168A1 (en) | 2008-06-17 | 2011-03-31 | Nitzan Rosenfeld | Methods for distinguishing between specific types of lung cancers |
GB0904957D0 (en) | 2009-03-23 | 2009-05-06 | Univ Erasmus Medical Ct | Tumour gene profile |
-
2005
- 2005-06-03 AU AU2005250495A patent/AU2005250495A1/en not_active Abandoned
- 2005-06-03 MX MXPA06014116A patent/MXPA06014116A/es unknown
- 2005-06-03 US US11/145,307 patent/US20060094035A1/en not_active Abandoned
- 2005-06-03 ES ES10011848.8T patent/ES2682466T3/es active Active
- 2005-06-03 DK DK05804887.7T patent/DK1751313T3/da active
- 2005-06-03 WO PCT/US2005/019736 patent/WO2005118879A2/en active Application Filing
- 2005-06-03 KR KR1020077000268A patent/KR20070057761A/ko not_active Application Discontinuation
- 2005-06-03 ES ES05804887.7T patent/ES2548514T3/es active Active
- 2005-06-03 JP JP2007515665A patent/JP5690039B2/ja active Active
- 2005-06-03 CA CA002569531A patent/CA2569531A1/en not_active Abandoned
- 2005-06-03 CN CNA2005800263805A patent/CN101035909A/zh active Pending
- 2005-06-03 EP EP10011848.8A patent/EP2371969B1/en not_active Not-in-force
- 2005-06-03 EP EP05804887.7A patent/EP1751313B1/en active Active
-
2006
- 2006-12-04 IL IL179811A patent/IL179811A/en active IP Right Grant
-
2012
- 2012-09-25 US US13/626,078 patent/US20130023441A1/en not_active Abandoned
-
2013
- 2013-10-04 JP JP2013209489A patent/JP5878904B2/ja active Active
-
2016
- 2016-12-02 US US15/368,411 patent/US10538816B2/en active Active
-
2019
- 2019-12-02 US US16/701,000 patent/US20200190597A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
CA2569531A1 (en) | 2005-12-15 |
JP5690039B2 (ja) | 2015-03-25 |
EP1751313A2 (en) | 2007-02-14 |
KR20070057761A (ko) | 2007-06-07 |
US20170268064A1 (en) | 2017-09-21 |
MXPA06014116A (es) | 2007-08-08 |
DK1751313T3 (da) | 2015-10-26 |
US10538816B2 (en) | 2020-01-21 |
EP2371969B1 (en) | 2018-05-23 |
AU2005250495A1 (en) | 2005-12-15 |
ES2682466T3 (es) | 2018-09-20 |
WO2005118879A2 (en) | 2005-12-15 |
IL179811A (en) | 2017-10-31 |
EP2371969A1 (en) | 2011-10-05 |
US20130023441A1 (en) | 2013-01-24 |
JP2014183838A (ja) | 2014-10-02 |
ES2548514T3 (es) | 2015-10-19 |
US20060094035A1 (en) | 2006-05-04 |
WO2005118879A3 (en) | 2006-04-13 |
EP1751313B1 (en) | 2015-07-22 |
IL179811A0 (en) | 2007-05-15 |
US20200190597A1 (en) | 2020-06-18 |
JP2008501345A (ja) | 2008-01-24 |
CN101035909A (zh) | 2007-09-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20230023867A1 (en) | Identification of tumors and tissues | |
JP5878904B2 (ja) | 腫瘍の同定 | |
US20230287511A1 (en) | Neuroendocrine tumors | |
JP6257125B2 (ja) | 疾患診断のための分子プロファイリングの方法および組成物 | |
JP2020108402A (ja) | 甲状腺状態の診断のための方法および組成物 | |
EP2121988B1 (en) | Prostate cancer survival and recurrence | |
US20180073085A1 (en) | Determining tumor origin | |
WO2013002750A2 (en) | Determining tumor origin | |
US20220106646A1 (en) | Determining tumor origin | |
US20090215037A1 (en) | Dynamically expressed genes with reduced redundancy | |
MX2007015252A (en) | Identification of tumors and tissues |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20140822 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20141003 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150120 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150416 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150818 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151215 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20151222 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160119 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160129 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5878904 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |