JP2008506407A - 乳房細胞増殖性疾患を検出するためのエピジェネティックな方法および核酸 - Google Patents
乳房細胞増殖性疾患を検出するためのエピジェネティックな方法および核酸 Download PDFInfo
- Publication number
- JP2008506407A JP2008506407A JP2007521881A JP2007521881A JP2008506407A JP 2008506407 A JP2008506407 A JP 2008506407A JP 2007521881 A JP2007521881 A JP 2007521881A JP 2007521881 A JP2007521881 A JP 2007521881A JP 2008506407 A JP2008506407 A JP 2008506407A
- Authority
- JP
- Japan
- Prior art keywords
- seq
- sequence
- methylation
- nucleic acid
- gene
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 199
- 210000000481 breast Anatomy 0.000 title claims abstract description 127
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 105
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 95
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 95
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 87
- 230000002062 proliferating effect Effects 0.000 title claims abstract description 54
- 201000010099 disease Diseases 0.000 title claims description 68
- 230000001973 epigenetic effect Effects 0.000 title description 8
- 238000007069 methylation reaction Methods 0.000 claims abstract description 231
- 230000011987 methylation Effects 0.000 claims abstract description 222
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 161
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 116
- 108020004414 DNA Proteins 0.000 claims description 161
- -1 SEQ ID NO: 26 Proteins 0.000 claims description 141
- 208000026310 Breast neoplasm Diseases 0.000 claims description 127
- 206010006187 Breast cancer Diseases 0.000 claims description 126
- 108091034117 Oligonucleotide Proteins 0.000 claims description 124
- 238000003556 assay Methods 0.000 claims description 99
- 239000003153 chemical reaction reagent Substances 0.000 claims description 91
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 82
- 239000002773 nucleotide Substances 0.000 claims description 71
- 125000003729 nucleotide group Chemical group 0.000 claims description 71
- 210000004027 cell Anatomy 0.000 claims description 70
- 101001109685 Homo sapiens Nuclear receptor subfamily 5 group A member 2 Proteins 0.000 claims description 63
- 102100022669 Nuclear receptor subfamily 5 group A member 2 Human genes 0.000 claims description 63
- 230000000295 complement effect Effects 0.000 claims description 61
- 108091029430 CpG site Proteins 0.000 claims description 59
- 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 claims description 59
- 230000003321 amplification Effects 0.000 claims description 59
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 59
- 210000001519 tissue Anatomy 0.000 claims description 51
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 49
- 238000009396 hybridization Methods 0.000 claims description 42
- 238000003752 polymerase chain reaction Methods 0.000 claims description 42
- 210000004369 blood Anatomy 0.000 claims description 40
- 239000008280 blood Substances 0.000 claims description 40
- 238000011282 treatment Methods 0.000 claims description 37
- 101000651890 Homo sapiens Slit homolog 2 protein Proteins 0.000 claims description 35
- 101000651893 Homo sapiens Slit homolog 3 protein Proteins 0.000 claims description 35
- 102100027340 Slit homolog 2 protein Human genes 0.000 claims description 35
- 238000006243 chemical reaction Methods 0.000 claims description 33
- 102100029647 Apoptosis-associated speck-like protein containing a CARD Human genes 0.000 claims description 32
- 102100024450 Prostaglandin E2 receptor EP4 subtype Human genes 0.000 claims description 32
- 102100024185 G1/S-specific cyclin-D2 Human genes 0.000 claims description 31
- 101000687346 Homo sapiens PR domain zinc finger protein 2 Proteins 0.000 claims description 31
- 101000739160 Homo sapiens Secretoglobin family 3A member 1 Proteins 0.000 claims description 31
- 101710195838 Prostaglandin E2 receptor EP4 subtype Proteins 0.000 claims description 31
- 102100037268 Secretoglobin family 3A member 1 Human genes 0.000 claims description 31
- 102100024885 PR domain zinc finger protein 2 Human genes 0.000 claims description 30
- 102100030943 Glutathione S-transferase P Human genes 0.000 claims description 29
- 101001010139 Homo sapiens Glutathione S-transferase P Proteins 0.000 claims description 29
- 102100026023 LIM domain kinase 1 Human genes 0.000 claims description 29
- 101710107718 LIM domain kinase 1 Proteins 0.000 claims description 29
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 29
- 108091093037 Peptide nucleic acid Proteins 0.000 claims description 29
- 101000980741 Homo sapiens G1/S-specific cyclin-D2 Proteins 0.000 claims description 28
- 102100031358 Urokinase-type plasminogen activator Human genes 0.000 claims description 28
- 102100038587 Death-associated protein kinase 1 Human genes 0.000 claims description 26
- 102100037738 Fatty acid-binding protein, heart Human genes 0.000 claims description 26
- 101000956145 Homo sapiens Death-associated protein kinase 1 Proteins 0.000 claims description 26
- 101001027663 Homo sapiens Fatty acid-binding protein, heart Proteins 0.000 claims description 26
- 101000638886 Homo sapiens Urokinase-type plasminogen activator Proteins 0.000 claims description 26
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 26
- 230000014509 gene expression Effects 0.000 claims description 26
- 102100034119 ADP-ribosylhydrolase ARH1 Human genes 0.000 claims description 25
- 102100037948 GTP-binding protein Di-Ras3 Human genes 0.000 claims description 25
- 102100025110 Homeobox protein Hox-A5 Human genes 0.000 claims description 25
- 101000780532 Homo sapiens ADP-ribosylhydrolase ARH1 Proteins 0.000 claims description 25
- 101000951235 Homo sapiens GTP-binding protein Di-Ras3 Proteins 0.000 claims description 25
- 101001077568 Homo sapiens Homeobox protein Hox-A5 Proteins 0.000 claims description 25
- 101000840577 Homo sapiens Insulin-like growth factor-binding protein 7 Proteins 0.000 claims description 25
- 101001038339 Homo sapiens LIM homeobox transcription factor 1-alpha Proteins 0.000 claims description 25
- 102100029228 Insulin-like growth factor-binding protein 7 Human genes 0.000 claims description 25
- 102100040290 LIM homeobox transcription factor 1-alpha Human genes 0.000 claims description 25
- 102100038595 Estrogen receptor Human genes 0.000 claims description 24
- 101000633503 Homo sapiens Nuclear receptor subfamily 2 group E member 1 Proteins 0.000 claims description 24
- 102100029534 Nuclear receptor subfamily 2 group E member 1 Human genes 0.000 claims description 24
- 101001124901 Homo sapiens Putative histone-lysine N-methyltransferase PRDM6 Proteins 0.000 claims description 23
- 102100029134 Putative histone-lysine N-methyltransferase PRDM6 Human genes 0.000 claims description 23
- 102100024154 Cadherin-13 Human genes 0.000 claims description 22
- 101000762243 Homo sapiens Cadherin-13 Proteins 0.000 claims description 22
- 102100023934 Heparan sulfate glucosamine 3-O-sulfotransferase 2 Human genes 0.000 claims description 21
- 101001048053 Homo sapiens Heparan sulfate glucosamine 3-O-sulfotransferase 2 Proteins 0.000 claims description 21
- 239000012634 fragment Substances 0.000 claims description 21
- ONCZDRURRATYFI-QTCHDTBASA-N methyl (2z)-2-methoxyimino-2-[2-[[(e)-1-[3-(trifluoromethyl)phenyl]ethylideneamino]oxymethyl]phenyl]acetate Chemical compound CO\N=C(/C(=O)OC)C1=CC=CC=C1CO\N=C(/C)C1=CC=CC(C(F)(F)F)=C1 ONCZDRURRATYFI-QTCHDTBASA-N 0.000 claims description 21
- 108700020463 BRCA1 Proteins 0.000 claims description 20
- 102000036365 BRCA1 Human genes 0.000 claims description 20
- 101150072950 BRCA1 gene Proteins 0.000 claims description 20
- 102100037156 Gap junction beta-2 protein Human genes 0.000 claims description 20
- 101000954092 Homo sapiens Gap junction beta-2 protein Proteins 0.000 claims description 20
- 101000659879 Homo sapiens Thrombospondin-1 Proteins 0.000 claims description 20
- 108010005173 SERPIN-B5 Proteins 0.000 claims description 20
- 102100030333 Serpin B5 Human genes 0.000 claims description 20
- 102100036034 Thrombospondin-1 Human genes 0.000 claims description 20
- 102100037674 Bis(5'-adenosyl)-triphosphatase Human genes 0.000 claims description 19
- 108010072135 Cell Adhesion Molecule-1 Proteins 0.000 claims description 19
- 102100024649 Cell adhesion molecule 1 Human genes 0.000 claims description 19
- 108010016788 Cyclin-Dependent Kinase Inhibitor p21 Proteins 0.000 claims description 19
- 102100033270 Cyclin-dependent kinase inhibitor 1 Human genes 0.000 claims description 19
- 102100030910 Eyes absent homolog 4 Human genes 0.000 claims description 19
- 102100033798 Homeobox protein aristaless-like 4 Human genes 0.000 claims description 19
- 101000938422 Homo sapiens Eyes absent homolog 4 Proteins 0.000 claims description 19
- 101000779608 Homo sapiens Homeobox protein aristaless-like 4 Proteins 0.000 claims description 19
- 102100026261 Metalloproteinase inhibitor 3 Human genes 0.000 claims description 19
- 108010031429 Tissue Inhibitor of Metalloproteinase-3 Proteins 0.000 claims description 19
- 108010005713 bis(5'-adenosyl)triphosphatase Proteins 0.000 claims description 19
- 229940104302 cytosine Drugs 0.000 claims description 18
- 102100038205 ATP-dependent RNA helicase DDX51 Human genes 0.000 claims description 17
- 108010009392 Cyclin-Dependent Kinase Inhibitor p16 Proteins 0.000 claims description 17
- 102100029951 Estrogen receptor beta Human genes 0.000 claims description 17
- 101000883797 Homo sapiens ATP-dependent RNA helicase DDX51 Proteins 0.000 claims description 17
- 101001010910 Homo sapiens Estrogen receptor beta Proteins 0.000 claims description 17
- 101000937642 Homo sapiens Malonyl-CoA-acyl carrier protein transacylase, mitochondrial Proteins 0.000 claims description 17
- 101000590830 Homo sapiens Monocarboxylate transporter 1 Proteins 0.000 claims description 17
- 102100027329 Malonyl-CoA-acyl carrier protein transacylase, mitochondrial Human genes 0.000 claims description 17
- 102100033455 TGF-beta receptor type-2 Human genes 0.000 claims description 17
- 108010082684 Transforming Growth Factor-beta Type II Receptor Proteins 0.000 claims description 17
- 102100022886 ADP-ribosylation factor-like protein 4C Human genes 0.000 claims description 16
- 101100482081 Agrobacterium vitis (strain S4 / ATCC BAA-846) iaaM gene Proteins 0.000 claims description 16
- 102100034524 Apoptotic protease-activating factor 1 Human genes 0.000 claims description 16
- 101100170834 Arabidopsis thaliana ERDJ3A gene Proteins 0.000 claims description 16
- 102100025657 Cilia- and flagella-associated protein 47 Human genes 0.000 claims description 16
- 102100021088 Homeobox protein Hox-B13 Human genes 0.000 claims description 16
- 102100027893 Homeobox protein Nkx-2.1 Human genes 0.000 claims description 16
- 101000974390 Homo sapiens ADP-ribosylation factor-like protein 4C Proteins 0.000 claims description 16
- 101000924629 Homo sapiens Apoptotic protease-activating factor 1 Proteins 0.000 claims description 16
- 101000914165 Homo sapiens Cilia- and flagella-associated protein 47 Proteins 0.000 claims description 16
- 101001041145 Homo sapiens Homeobox protein Hox-B13 Proteins 0.000 claims description 16
- 101000993380 Homo sapiens Hypermethylated in cancer 1 protein Proteins 0.000 claims description 16
- 101100110004 Homo sapiens PYCARD gene Proteins 0.000 claims description 16
- 101000735377 Homo sapiens Protocadherin-7 Proteins 0.000 claims description 16
- 101000684503 Homo sapiens Sentrin-specific protease 3 Proteins 0.000 claims description 16
- 101000712600 Homo sapiens Thyroid hormone receptor beta Proteins 0.000 claims description 16
- 101000604583 Homo sapiens Tyrosine-protein kinase SYK Proteins 0.000 claims description 16
- 102100031612 Hypermethylated in cancer 1 protein Human genes 0.000 claims description 16
- 101100095608 Mus musculus Serinc3 gene Proteins 0.000 claims description 16
- 102000011367 Prostanoid EP4 receptors Human genes 0.000 claims description 16
- 108050001693 Prostanoid EP4 receptors Proteins 0.000 claims description 16
- 102100034941 Protocadherin-7 Human genes 0.000 claims description 16
- 108010044012 STAT1 Transcription Factor Proteins 0.000 claims description 16
- 102100023645 Sentrin-specific protease 3 Human genes 0.000 claims description 16
- 102100029904 Signal transducer and activator of transcription 1-alpha/beta Human genes 0.000 claims description 16
- 108010087999 Steryl-Sulfatase Proteins 0.000 claims description 16
- 108010057722 Synaptosomal-Associated Protein 25 Proteins 0.000 claims description 16
- 102100030552 Synaptosomal-associated protein 25 Human genes 0.000 claims description 16
- 108010057966 Thyroid Nuclear Factor 1 Proteins 0.000 claims description 16
- 102100033451 Thyroid hormone receptor beta Human genes 0.000 claims description 16
- 102100038183 Tyrosine-protein kinase SYK Human genes 0.000 claims description 16
- 101150116154 tms1 gene Proteins 0.000 claims description 16
- 102100037985 Dickkopf-related protein 3 Human genes 0.000 claims description 15
- 101000951342 Homo sapiens Dickkopf-related protein 3 Proteins 0.000 claims description 15
- 108090000629 orphan nuclear receptors Proteins 0.000 claims description 15
- 102000004164 orphan nuclear receptors Human genes 0.000 claims description 15
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 14
- 102100021239 G protein-activated inward rectifier potassium channel 2 Human genes 0.000 claims description 14
- 101000614714 Homo sapiens G protein-activated inward rectifier potassium channel 2 Proteins 0.000 claims description 14
- 101000979629 Homo sapiens Nucleoside diphosphate kinase A Proteins 0.000 claims description 14
- 101000734351 Homo sapiens PDZ and LIM domain protein 1 Proteins 0.000 claims description 14
- 101000657452 Homo sapiens Rotatin Proteins 0.000 claims description 14
- 102100023252 Nucleoside diphosphate kinase A Human genes 0.000 claims description 14
- 102100034819 PDZ and LIM domain protein 1 Human genes 0.000 claims description 14
- 102100033909 Retinoic acid receptor beta Human genes 0.000 claims description 14
- 102100034742 Rotatin Human genes 0.000 claims description 14
- 108010091356 Tumor Protein p73 Proteins 0.000 claims description 14
- 102100030018 Tumor protein p73 Human genes 0.000 claims description 14
- 239000012472 biological sample Substances 0.000 claims description 14
- 102100026098 Claudin-7 Human genes 0.000 claims description 13
- 102100032530 Glypican-3 Human genes 0.000 claims description 13
- 101000912652 Homo sapiens Claudin-7 Proteins 0.000 claims description 13
- 101001014668 Homo sapiens Glypican-3 Proteins 0.000 claims description 13
- 101001132698 Homo sapiens Retinoic acid receptor beta Proteins 0.000 claims description 13
- 101000730643 Homo sapiens Zinc finger protein PLAGL1 Proteins 0.000 claims description 13
- 102000004889 Interleukin-6 Human genes 0.000 claims description 13
- 108090001005 Interleukin-6 Proteins 0.000 claims description 13
- 108010005256 S100 Calcium Binding Protein A7 Proteins 0.000 claims description 13
- 102100032570 Zinc finger protein PLAGL1 Human genes 0.000 claims description 13
- 229940035893 uracil Drugs 0.000 claims description 13
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 claims description 12
- 102100026548 Caspase-8 Human genes 0.000 claims description 12
- 102100032920 Chromobox protein homolog 2 Human genes 0.000 claims description 12
- 102100025615 Gamma-synuclein Human genes 0.000 claims description 12
- 101710083165 Glutamine synthetase cytosolic isozyme Proteins 0.000 claims description 12
- 101000983528 Homo sapiens Caspase-8 Proteins 0.000 claims description 12
- 101000797586 Homo sapiens Chromobox protein homolog 2 Proteins 0.000 claims description 12
- 101000882584 Homo sapiens Estrogen receptor Proteins 0.000 claims description 12
- 101000787273 Homo sapiens Gamma-synuclein Proteins 0.000 claims description 12
- 101000693721 Homo sapiens SAM and SH3 domain-containing protein 1 Proteins 0.000 claims description 12
- 102100029753 Reduced folate transporter Human genes 0.000 claims description 12
- 102100025543 SAM and SH3 domain-containing protein 1 Human genes 0.000 claims description 12
- 108091006778 SLC19A1 Proteins 0.000 claims description 12
- 102100032891 Superoxide dismutase [Mn], mitochondrial Human genes 0.000 claims description 12
- 102000003998 progesterone receptors Human genes 0.000 claims description 12
- 108090000468 progesterone receptors Proteins 0.000 claims description 12
- 108010045815 superoxide dismutase 2 Proteins 0.000 claims description 12
- 108091008146 restriction endonucleases Proteins 0.000 claims description 11
- 238000012163 sequencing technique Methods 0.000 claims description 11
- 102100027833 14-3-3 protein sigma Human genes 0.000 claims description 10
- 102100022983 B-cell lymphoma/leukemia 11B Human genes 0.000 claims description 10
- 101000903697 Homo sapiens B-cell lymphoma/leukemia 11B Proteins 0.000 claims description 10
- 210000002381 plasma Anatomy 0.000 claims description 10
- 102100028843 DNA mismatch repair protein Mlh1 Human genes 0.000 claims description 9
- 108010026664 MutL Protein Homolog 1 Proteins 0.000 claims description 9
- 102100023606 Retinoic acid receptor alpha Human genes 0.000 claims description 9
- 210000000601 blood cell Anatomy 0.000 claims description 9
- 238000012545 processing Methods 0.000 claims description 9
- 210000002966 serum Anatomy 0.000 claims description 9
- 102000004190 Enzymes Human genes 0.000 claims description 8
- 108090000790 Enzymes Proteins 0.000 claims description 8
- 101000723509 Homo sapiens 14-3-3 protein sigma Proteins 0.000 claims description 8
- 101001130862 Homo sapiens Oligoribonuclease, mitochondrial Proteins 0.000 claims description 8
- 101001125574 Homo sapiens Prostasin Proteins 0.000 claims description 8
- 101001130437 Homo sapiens Ras-related protein Rap-2b Proteins 0.000 claims description 8
- 102100029500 Prostasin Human genes 0.000 claims description 8
- 102100031421 Ras-related protein Rap-2b Human genes 0.000 claims description 8
- 102000005871 S100 Calcium Binding Protein A7 Human genes 0.000 claims description 8
- 230000002441 reversible effect Effects 0.000 claims description 8
- 239000007790 solid phase Substances 0.000 claims description 8
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 claims description 7
- 238000011002 quantification Methods 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 6
- 108700020462 BRCA2 Proteins 0.000 claims description 5
- 102000052609 BRCA2 Human genes 0.000 claims description 5
- 101150008921 Brca2 gene Proteins 0.000 claims description 5
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 claims description 5
- 101000801701 Homo sapiens Tropomyosin alpha-1 chain Proteins 0.000 claims description 5
- 206010073094 Intraductal proliferative breast lesion Diseases 0.000 claims description 5
- 102100033632 Tropomyosin alpha-1 chain Human genes 0.000 claims description 5
- 108091007854 Cdh1/Fizzy-related Proteins 0.000 claims description 4
- 102000038594 Cdh1/Fizzy-related Human genes 0.000 claims description 4
- 210000002751 lymph Anatomy 0.000 claims description 4
- 210000002445 nipple Anatomy 0.000 claims description 4
- 101001027128 Homo sapiens Fibronectin Proteins 0.000 claims description 3
- 101001123332 Homo sapiens Proteoglycan 4 Proteins 0.000 claims description 3
- 101000632056 Homo sapiens Septin-9 Proteins 0.000 claims description 3
- 108091000080 Phosphotransferase Proteins 0.000 claims description 3
- 102100028024 Septin-9 Human genes 0.000 claims description 3
- 102000020233 phosphotransferase Human genes 0.000 claims description 3
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 claims description 2
- 108060002716 Exonuclease Proteins 0.000 claims description 2
- 101001112293 Homo sapiens Retinoic acid receptor alpha Proteins 0.000 claims description 2
- 102000013165 exonuclease Human genes 0.000 claims description 2
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 claims 6
- 102100032250 Trichohyalin Human genes 0.000 claims 6
- 108010031667 trichohyalin Proteins 0.000 claims 6
- 102100039391 Pseudouridine-5'-phosphatase Human genes 0.000 claims 4
- 102100031457 Collagen alpha-1(V) chain Human genes 0.000 claims 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 claims 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 claims 1
- 101000941708 Homo sapiens Collagen alpha-1(V) chain Proteins 0.000 claims 1
- 101000972291 Homo sapiens Lymphoid enhancer-binding factor 1 Proteins 0.000 claims 1
- 101000760183 Homo sapiens Zinc finger protein 44 Proteins 0.000 claims 1
- 102100022699 Lymphoid enhancer-binding factor 1 Human genes 0.000 claims 1
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 claims 1
- 102100024660 Zinc finger protein 44 Human genes 0.000 claims 1
- 239000012503 blood component Substances 0.000 claims 1
- 208000011803 breast fibrocystic disease Diseases 0.000 abstract description 13
- 208000030270 breast disease Diseases 0.000 abstract description 2
- 239000000523 sample Substances 0.000 description 130
- 238000004458 analytical method Methods 0.000 description 76
- 238000001514 detection method Methods 0.000 description 74
- 201000011510 cancer Diseases 0.000 description 61
- 238000012360 testing method Methods 0.000 description 58
- 239000011159 matrix material Substances 0.000 description 50
- 208000037396 Intraductal Noninfiltrating Carcinoma Diseases 0.000 description 41
- 208000028715 ductal breast carcinoma in situ Diseases 0.000 description 34
- 230000035945 sensitivity Effects 0.000 description 31
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 30
- 239000003550 marker Substances 0.000 description 30
- 238000004925 denaturation Methods 0.000 description 26
- 230000036425 denaturation Effects 0.000 description 26
- 238000007855 methylation-specific PCR Methods 0.000 description 25
- 238000010195 expression analysis Methods 0.000 description 24
- 238000002493 microarray Methods 0.000 description 24
- 238000012216 screening Methods 0.000 description 24
- 238000009826 distribution Methods 0.000 description 23
- 102000004169 proteins and genes Human genes 0.000 description 22
- 239000000047 product Substances 0.000 description 19
- 239000000538 analytical sample Substances 0.000 description 18
- 108090000765 processed proteins & peptides Proteins 0.000 description 18
- 238000012207 quantitative assay Methods 0.000 description 18
- 102100033254 Tumor suppressor ARF Human genes 0.000 description 17
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 17
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 17
- 230000008569 process Effects 0.000 description 17
- 230000000875 corresponding effect Effects 0.000 description 16
- 208000035475 disorder Diseases 0.000 description 16
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 16
- 229910001629 magnesium chloride Inorganic materials 0.000 description 15
- 238000009607 mammography Methods 0.000 description 15
- 108020004999 messenger RNA Proteins 0.000 description 15
- 230000000903 blocking effect Effects 0.000 description 14
- 210000001124 body fluid Anatomy 0.000 description 14
- 238000003745 diagnosis Methods 0.000 description 14
- 210000004698 lymphocyte Anatomy 0.000 description 14
- 238000000137 annealing Methods 0.000 description 13
- 239000010839 body fluid Substances 0.000 description 13
- 239000000872 buffer Substances 0.000 description 13
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 12
- 206010001233 Adenoma benign Diseases 0.000 description 12
- 230000007067 DNA methylation Effects 0.000 description 12
- 208000007659 Fibroadenoma Diseases 0.000 description 12
- 201000003149 breast fibroadenoma Diseases 0.000 description 12
- 108010038795 estrogen receptors Proteins 0.000 description 12
- 239000012530 fluid Substances 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 108091029523 CpG island Proteins 0.000 description 11
- 238000011161 development Methods 0.000 description 11
- 230000018109 developmental process Effects 0.000 description 11
- 238000002405 diagnostic procedure Methods 0.000 description 11
- 230000002068 genetic effect Effects 0.000 description 11
- 230000001105 regulatory effect Effects 0.000 description 11
- 238000007473 univariate analysis Methods 0.000 description 11
- 238000007403 mPCR Methods 0.000 description 10
- 229920001184 polypeptide Polymers 0.000 description 10
- 239000002131 composite material Substances 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 9
- 238000007477 logistic regression Methods 0.000 description 9
- 210000000019 nipple aspirate fluid Anatomy 0.000 description 9
- 208000000571 Fibrocystic breast disease Diseases 0.000 description 8
- 102100030409 Unconventional myosin-Va Human genes 0.000 description 8
- 230000002159 abnormal effect Effects 0.000 description 8
- 230000000692 anti-sense effect Effects 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 210000001165 lymph node Anatomy 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 8
- 206010006256 Breast hyperplasia Diseases 0.000 description 7
- 238000012937 correction Methods 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 238000004393 prognosis Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 231100000504 carcinogenesis Toxicity 0.000 description 6
- 230000004069 differentiation Effects 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 230000006607 hypermethylation Effects 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 238000010202 multivariate logistic regression analysis Methods 0.000 description 6
- 239000013610 patient sample Substances 0.000 description 6
- 238000000513 principal component analysis Methods 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 208000005623 Carcinogenesis Diseases 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 5
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 5
- 230000036952 cancer formation Effects 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 230000029087 digestion Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000001502 gel electrophoresis Methods 0.000 description 5
- 238000003018 immunoassay Methods 0.000 description 5
- 238000002372 labelling Methods 0.000 description 5
- 201000005202 lung cancer Diseases 0.000 description 5
- 208000020816 lung neoplasm Diseases 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 102000054765 polymorphisms of proteins Human genes 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000000108 ultra-filtration Methods 0.000 description 5
- 206010002329 Aneurysm Diseases 0.000 description 4
- 230000030933 DNA methylation on cytosine Effects 0.000 description 4
- 101000733249 Homo sapiens Tumor suppressor ARF Proteins 0.000 description 4
- 238000012408 PCR amplification Methods 0.000 description 4
- 208000002163 Phyllodes Tumor Diseases 0.000 description 4
- 206010071776 Phyllodes tumour Diseases 0.000 description 4
- 238000003070 Statistical process control Methods 0.000 description 4
- 239000012491 analyte Substances 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- 210000001072 colon Anatomy 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 238000002790 cross-validation Methods 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000010839 reverse transcription Methods 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 229940113082 thymine Drugs 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 108010058544 Cyclin D2 Proteins 0.000 description 3
- 238000000018 DNA microarray Methods 0.000 description 3
- 230000004568 DNA-binding Effects 0.000 description 3
- 108010067770 Endopeptidase K Proteins 0.000 description 3
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 238000002944 PCR assay Methods 0.000 description 3
- 108010006785 Taq Polymerase Proteins 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000009098 adjuvant therapy Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 201000007295 breast benign neoplasm Diseases 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical class C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 3
- 239000000356 contaminant Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000007405 data analysis Methods 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
- 150000002012 dioxanes Chemical class 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 239000007850 fluorescent dye Substances 0.000 description 3
- 230000000762 glandular Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 108091008039 hormone receptors Proteins 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 230000000984 immunochemical effect Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 208000004396 mastitis Diseases 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000002751 oligonucleotide probe Substances 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 238000003672 processing method Methods 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 238000005185 salting out Methods 0.000 description 3
- 238000007423 screening assay Methods 0.000 description 3
- 238000012706 support-vector machine Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 108050008974 14-3-3 protein sigma Proteins 0.000 description 2
- 102100023635 Alpha-fetoprotein Human genes 0.000 description 2
- 101710083889 Alpha-fetoprotein Proteins 0.000 description 2
- 241000272194 Ciconiiformes Species 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- BVTJGGGYKAMDBN-UHFFFAOYSA-N Dioxetane Chemical class C1COO1 BVTJGGGYKAMDBN-UHFFFAOYSA-N 0.000 description 2
- 208000006402 Ductal Carcinoma Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102100031780 Endonuclease Human genes 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 206010064571 Gene mutation Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 241000102542 Kara Species 0.000 description 2
- 208000000265 Lobular Carcinoma Diseases 0.000 description 2
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 2
- 101100329880 Mus musculus Cyb561 gene Proteins 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 208000010191 Osteitis Deformans Diseases 0.000 description 2
- 208000027868 Paget disease Diseases 0.000 description 2
- 241000276498 Pollachius virens Species 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 101710163352 Potassium voltage-gated channel subfamily H member 4 Proteins 0.000 description 2
- 102100024231 SH3KBP1-binding protein 1 Human genes 0.000 description 2
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 2
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 2
- 108010079351 Tumor Suppressor Protein p14ARF Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004520 agglutination Effects 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- 238000013528 artificial neural network Methods 0.000 description 2
- 201000003714 breast lobular carcinoma Diseases 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000003795 desorption Methods 0.000 description 2
- 230000006326 desulfonation Effects 0.000 description 2
- 238000005869 desulfonation reaction Methods 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 210000004696 endometrium Anatomy 0.000 description 2
- 238000001976 enzyme digestion Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000001917 fluorescence detection Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 208000030776 invasive breast carcinoma Diseases 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 208000027202 mammary Paget disease Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000009245 menopause Effects 0.000 description 2
- 238000010208 microarray analysis Methods 0.000 description 2
- 238000003909 pattern recognition Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000005375 photometry Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000007781 pre-processing Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000011897 real-time detection Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000011896 sensitive detection Methods 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000006277 sulfonation reaction Methods 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- HWPZZUQOWRWFDB-UHFFFAOYSA-N 1-methylcytosine Chemical compound CN1C=CC(N)=NC1=O HWPZZUQOWRWFDB-UHFFFAOYSA-N 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 102100036441 Amyloid-beta A4 precursor protein-binding family A member 2 Human genes 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 206010006253 Breast fibrosis Diseases 0.000 description 1
- 206010006298 Breast pain Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 102000004410 Cholesterol 7-alpha-monooxygenases Human genes 0.000 description 1
- 108090000943 Cholesterol 7-alpha-monooxygenases Proteins 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 230000007064 DNA hydrolysis Effects 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 101000928677 Homo sapiens Amyloid-beta A4 precursor protein-binding family A member 2 Proteins 0.000 description 1
- 206010073099 Lobular breast carcinoma in situ Diseases 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 208000006662 Mastodynia Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000012868 Overgrowth Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 102100025067 Potassium voltage-gated channel subfamily H member 4 Human genes 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 101150007311 S100A7 gene Proteins 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- GLEVLJDDWXEYCO-UHFFFAOYSA-N Trolox Chemical compound O1C(C)(C(O)=O)CCC2=C1C(C)=C(C)C(O)=C2C GLEVLJDDWXEYCO-UHFFFAOYSA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 101150010487 are gene Proteins 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 201000005389 breast carcinoma in situ Diseases 0.000 description 1
- 210000000069 breast epithelial cell Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 208000012106 cystic neoplasm Diseases 0.000 description 1
- 230000002380 cytological effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000009261 endocrine therapy Methods 0.000 description 1
- 229940034984 endocrine therapy antineoplastic and immunomodulating agent Drugs 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 230000006718 epigenetic regulation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000004996 female reproductive system Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 238000003208 gene overexpression Methods 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 201000006604 granular cell tumor Diseases 0.000 description 1
- ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 230000006195 histone acetylation Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000000951 immunodiffusion Effects 0.000 description 1
- 238000000760 immunoelectrophoresis Methods 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 238000000752 ionisation method Methods 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000010339 medical test Methods 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012775 microarray technology Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000005528 milk analysis Methods 0.000 description 1
- 230000033607 mismatch repair Effects 0.000 description 1
- 208000016044 mixed lobular and ductal breast carcinoma Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000013188 needle biopsy Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 238000003499 nucleic acid array Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000009595 pap smear Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical group 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 238000013439 planning Methods 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000768 polyamine Chemical group 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000012113 quantitative test Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 238000010223 real-time analysis Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000037425 regulation of transcription Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 108091008761 retinoic acid receptors β Proteins 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical group [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
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
-
- 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
- C12Q2600/154—Methylation markers
-
- 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
-
- 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
- C12Q2600/16—Primer sets for multiplex assays
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Hospice & Palliative Care (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04016926 | 2004-07-18 | ||
| PCT/EP2005/007830 WO2006008128A2 (en) | 2004-07-18 | 2005-07-18 | Epigenetic methods and nucleic acids for the detection of breast cell proliferative disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008506407A true JP2008506407A (ja) | 2008-03-06 |
| JP2008506407A5 JP2008506407A5 (enExample) | 2008-09-25 |
Family
ID=35462310
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007521881A Pending JP2008506407A (ja) | 2004-07-18 | 2005-07-18 | 乳房細胞増殖性疾患を検出するためのエピジェネティックな方法および核酸 |
Country Status (4)
| Country | Link |
|---|---|
| US (2) | US20090298054A1 (enExample) |
| EP (4) | EP2281902A1 (enExample) |
| JP (1) | JP2008506407A (enExample) |
| WO (1) | WO2006008128A2 (enExample) |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011105570A1 (ja) | 2010-02-26 | 2011-09-01 | シスメックス株式会社 | 生体試料中の癌細胞の存否を判定する方法、判定用分子マーカーおよびキット |
| JP2011177058A (ja) * | 2010-02-26 | 2011-09-15 | Meiji Co Ltd | 消化管癌に対する発癌リスク抑制効果の評価方法 |
| JP2012517215A (ja) * | 2009-01-30 | 2012-08-02 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | 胸部腫瘍のサブ分類のための方法 |
| JPWO2010113529A1 (ja) * | 2009-04-03 | 2012-10-04 | 株式会社エイアンドティー | 大腸腫瘍の検出方法 |
| JP2012523828A (ja) * | 2009-04-17 | 2012-10-11 | ユニヴェルシテ リブル ドゥ ブリュッセル | ガンにおけるアントラサイクリン系薬剤の効率を予測するための方法およびツール |
| JP2013526869A (ja) * | 2010-05-28 | 2013-06-27 | ビオメリュー | 乳癌と良性乳房疾患を識別するための方法及びキット |
| JP2014513935A (ja) * | 2011-03-31 | 2014-06-19 | クイーン マリー アンド ウエストフィールド カレッジ、ユニバーシティ オブ ロンドン | がんマーカー |
| JP2017090103A (ja) * | 2015-11-05 | 2017-05-25 | 和光純薬工業株式会社 | 非浸潤性乳癌の判定法 |
| JP2017090102A (ja) * | 2015-11-05 | 2017-05-25 | 和光純薬工業株式会社 | 浸潤性乳癌の判定法 |
| JP2017537623A (ja) * | 2014-12-05 | 2017-12-21 | エピオンティス ゲーエムベーハー | 濾胞性ヘルパーｔ（ｔｆｈ）細胞を同定するためのエピジェネティック法 |
| WO2019054326A1 (ja) * | 2017-09-13 | 2019-03-21 | 三菱スペース・ソフトウエア株式会社 | コピー数計測装置、コピー数計測プログラム、コピー数計測方法および遺伝子パネル |
| JP2023513039A (ja) * | 2020-01-28 | 2023-03-30 | ジェンキュリクス インク | 特定の遺伝子のＣｐＧメチル化の変化を利用した膀胱癌診断用組成物およびその使用 |
| JP2023175696A (ja) * | 2019-04-30 | 2023-12-12 | 上▲海▼奕▲譜▼生物科技有限公司 | メチル化修飾に基づく腫瘍マーカーｓｔａｍｐ－ｅｐ９及びその応用 |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2533767T3 (es) * | 2005-04-15 | 2015-04-15 | Epigenomics Ag | Métodos para el análisis de trastornos proliferativos celulares |
| JP2007267700A (ja) * | 2006-03-31 | 2007-10-18 | Kochi Univ | Ｈｏｘｂ１３遺伝子のメチル化を指標とする腎細胞癌を含む悪性腫瘍の判定方法 |
| US20090317810A1 (en) * | 2006-04-17 | 2009-12-24 | Epigenomics Ag | Methods and nucleic acids for the detection of colorectal cell proliferative disorders |
| EP2013360A2 (en) * | 2006-04-17 | 2009-01-14 | Epigenomics AG | Methods and nucleic acids for the detection of colorectal cell proliferative disorders |
| EP2634264B1 (en) * | 2006-07-21 | 2016-09-14 | Epigenomics AG | Methods and nucleic acids related to the gene GLI3 for analyses of cellular proliferative disorders |
| WO2008009479A1 (en) * | 2006-07-21 | 2008-01-24 | Epigenomics Ag | Methods and nucleic acids for analyses for cellular proliferative disorders |
| ES2384071T3 (es) | 2007-01-19 | 2012-06-29 | Epigenomics Ag | Métodos y ácidos nucleicos para análisis de trastornos proliferativos celulares |
| US9096849B2 (en) * | 2007-05-21 | 2015-08-04 | The United States Of America, As Represented By The Secretary Of The Navy | Solid phase for capture of nucleic acids |
| RU2492243C2 (ru) * | 2007-09-17 | 2013-09-10 | Конинклейке Филипс Электроникс Н.В. | Способ анализа онкологических заболеваний молочной железы |
| JP5694776B2 (ja) * | 2007-12-11 | 2015-04-01 | エピゲノミクス アーゲー | 細胞増殖性障害の解析のための方法及び核酸 |
| WO2009074364A1 (en) * | 2007-12-13 | 2009-06-18 | Edgar Dahl | Novel prognostic breast cancer marker |
| EP2271774B1 (en) * | 2008-03-21 | 2018-03-07 | MDxHealth | Detection and prognosis of cervical cancer |
| JP2009247260A (ja) * | 2008-04-04 | 2009-10-29 | Sumitomo Chemical Co Ltd | Ｄｎａメチル化測定方法 |
| US20100112643A1 (en) * | 2008-11-04 | 2010-05-06 | The Government Of The United States Of America, As Represented By The Secretary Of The Navy | Method for direct capture of ribonucleic acid |
| US20120190024A1 (en) * | 2009-06-30 | 2012-07-26 | Sysmex Corporation | Method for determining presence or absence of epithelial cancer-origin cell in biological sample, and molecular marker and kit therefor |
| GB201000688D0 (en) * | 2010-01-15 | 2010-03-03 | Diagenic Asa | Product and method |
| US20130309667A1 (en) * | 2012-05-15 | 2013-11-21 | Anthony P. Shuber | Primers for analyzing methylated sequences and methods of use thereof |
| US9976187B2 (en) | 2012-06-13 | 2018-05-22 | King Abdullah University Of Science And Technology | Methylation biomarkers for prostate cancer |
| US9732390B2 (en) | 2012-09-20 | 2017-08-15 | The Chinese University Of Hong Kong | Non-invasive determination of methylome of fetus or tumor from plasma |
| US10706957B2 (en) | 2012-09-20 | 2020-07-07 | The Chinese University Of Hong Kong | Non-invasive determination of methylome of tumor from plasma |
| CA2914685A1 (en) | 2013-06-24 | 2014-12-31 | Mirna Therapeutics, Inc. | Biomarkers of mir-34 activity |
| WO2018009890A1 (en) * | 2016-07-08 | 2018-01-11 | Ontolead, Inc. | Relationship analysis utilizing biofeedback information |
| CN110225984A (zh) * | 2016-09-07 | 2019-09-10 | 科技研究局 | 鉴别癌症风险的方法和治疗选择 |
| CN107267597A (zh) * | 2017-03-10 | 2017-10-20 | 王建华 | Hic1在肿瘤诊断、治疗、预后和预测复发中的应用 |
| CA3067824C (en) * | 2017-06-26 | 2025-05-27 | Univ New York State Res Found | COMPUTER-ACCESSIBLE SYSTEM, METHOD, AND MEDIA FOR VIRTUAL PANCREATOGRAPHY |
| CN112567049A (zh) * | 2018-07-26 | 2021-03-26 | 北京艾克伦医疗科技有限公司 | 鉴定胃癌状态的方法和试剂盒 |
| EP3828290A4 (en) * | 2018-07-26 | 2022-03-23 | Excellen Medical Technology Co., Ltd. | Method for identifying state of breast cancer and kit |
| WO2020252721A1 (en) * | 2019-06-20 | 2020-12-24 | The Johns Hopkins University | Dna methylation markers and their use in differentiation of suspected cancerous lymph node biopsy samples |
| WO2025212993A1 (en) * | 2024-04-05 | 2025-10-09 | Encoded Therapeutics, Inc. | Materials and methods for trangene expression in neural cells |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002018632A2 (de) * | 2000-09-01 | 2002-03-07 | Epigenomics Ag | Verfahren zur bestimmung des methylierungsgrades von bestimmten cytosinen in genomischer dna im sequenzkontext 5'-cpg-3' |
| WO2004020662A2 (en) * | 2002-08-27 | 2004-03-11 | Epigenomics Ag | Method and nucleic acids for the analysis of breast cell proliferative disorders |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5585481A (en) | 1987-09-21 | 1996-12-17 | Gen-Probe Incorporated | Linking reagents for nucleotide probes |
| US5457183A (en) | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
| US5245022A (en) | 1990-08-03 | 1993-09-14 | Sterling Drug, Inc. | Exonuclease resistant terminally substituted oligonucleotides |
| US5565552A (en) | 1992-01-21 | 1996-10-15 | Pharmacyclics, Inc. | Method of expanded porphyrin-oligonucleotide conjugate synthesis |
| US5574142A (en) | 1992-12-15 | 1996-11-12 | Microprobe Corporation | Peptide linkers for improved oligonucleotide delivery |
| SE501439C2 (sv) | 1993-06-22 | 1995-02-13 | Pharmacia Lkb Biotech | Sätt och anordning för analys av polynukleotidsekvenser |
| DE69417918T2 (de) | 1993-11-30 | 2000-01-05 | Mcgill University, Montreal | Dna methyltransferase inhibierung |
| US5597696A (en) | 1994-07-18 | 1997-01-28 | Becton Dickinson And Company | Covalent cyanine dye oligonucleotide conjugates |
| US5514758A (en) | 1994-09-30 | 1996-05-07 | The Goodyear Tire & Rubber Company | Process for making latex for high performance masking tape |
| US6017704A (en) | 1996-06-03 | 2000-01-25 | The Johns Hopkins University School Of Medicine | Method of detection of methylated nucleic acid using agents which modify unmethylated cytosine and distinguishing modified methylated and non-methylated nucleic acids |
| US5786146A (en) | 1996-06-03 | 1998-07-28 | The Johns Hopkins University School Of Medicine | Method of detection of methylated nucleic acid using agents which modify unmethylated cytosine and distinguishing modified methylated and non-methylated nucleic acids |
| AU7829398A (en) | 1997-06-09 | 1998-12-30 | University Of Southern California | A cancer diagnostic method based upon dna methylation differences |
| DE19754482A1 (de) | 1997-11-27 | 1999-07-01 | Epigenomics Gmbh | Verfahren zur Herstellung komplexer DNA-Methylierungs-Fingerabdrücke |
| US7700324B1 (en) | 1998-11-03 | 2010-04-20 | The Johns Hopkins University School Of Medicine | Methylated CpG island amplification (MCA) |
| US5958773A (en) | 1998-12-17 | 1999-09-28 | Isis Pharmaceuticals Inc. | Antisense modulation of AKT-1 expression |
| US6331393B1 (en) | 1999-05-14 | 2001-12-18 | University Of Southern California | Process for high-throughput DNA methylation analysis |
| AU2001277521A1 (en) * | 2000-06-30 | 2002-01-14 | Epigenomics Ag | Diagnosis of diseases associated with cell signalling |
| DE10112515B4 (de) | 2001-03-09 | 2004-02-12 | Epigenomics Ag | Verfahren zum Nachweis von Cytosin-Methylierungsmustern mit hoher Sensitivität |
| US7473767B2 (en) | 2001-07-03 | 2009-01-06 | The Institute For Systems Biology | Methods for detection and quantification of analytes in complex mixtures |
| JP2005204651A (ja) * | 2003-12-11 | 2005-08-04 | Epigenomics Ag | 乳房細胞増殖障害の患者の治療応答及び／又は生存期間の予測のための予後診断マーカー |
-
2005
- 2005-07-18 EP EP10174950A patent/EP2281902A1/en not_active Withdrawn
- 2005-07-18 EP EP10174924A patent/EP2302073A1/en not_active Withdrawn
- 2005-07-18 JP JP2007521881A patent/JP2008506407A/ja active Pending
- 2005-07-18 EP EP05768093A patent/EP1769086A2/en not_active Withdrawn
- 2005-07-18 EP EP08009974A patent/EP1961827A3/en not_active Withdrawn
- 2005-07-18 US US11/632,824 patent/US20090298054A1/en not_active Abandoned
- 2005-07-18 WO PCT/EP2005/007830 patent/WO2006008128A2/en not_active Ceased
-
2011
- 2011-02-10 US US13/025,099 patent/US20110269126A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002018632A2 (de) * | 2000-09-01 | 2002-03-07 | Epigenomics Ag | Verfahren zur bestimmung des methylierungsgrades von bestimmten cytosinen in genomischer dna im sequenzkontext 5'-cpg-3' |
| WO2004020662A2 (en) * | 2002-08-27 | 2004-03-11 | Epigenomics Ag | Method and nucleic acids for the analysis of breast cell proliferative disorders |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012517215A (ja) * | 2009-01-30 | 2012-08-02 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | 胸部腫瘍のサブ分類のための方法 |
| JPWO2010113529A1 (ja) * | 2009-04-03 | 2012-10-04 | 株式会社エイアンドティー | 大腸腫瘍の検出方法 |
| JP2012523828A (ja) * | 2009-04-17 | 2012-10-11 | ユニヴェルシテ リブル ドゥ ブリュッセル | ガンにおけるアントラサイクリン系薬剤の効率を予測するための方法およびツール |
| WO2011105570A1 (ja) | 2010-02-26 | 2011-09-01 | シスメックス株式会社 | 生体試料中の癌細胞の存否を判定する方法、判定用分子マーカーおよびキット |
| JP2011177058A (ja) * | 2010-02-26 | 2011-09-15 | Meiji Co Ltd | 消化管癌に対する発癌リスク抑制効果の評価方法 |
| JP2013526869A (ja) * | 2010-05-28 | 2013-06-27 | ビオメリュー | 乳癌と良性乳房疾患を識別するための方法及びキット |
| JP2014513935A (ja) * | 2011-03-31 | 2014-06-19 | クイーン マリー アンド ウエストフィールド カレッジ、ユニバーシティ オブ ロンドン | がんマーカー |
| JP2017537623A (ja) * | 2014-12-05 | 2017-12-21 | エピオンティス ゲーエムベーハー | 濾胞性ヘルパーｔ（ｔｆｈ）細胞を同定するためのエピジェネティック法 |
| JP2017090103A (ja) * | 2015-11-05 | 2017-05-25 | 和光純薬工業株式会社 | 非浸潤性乳癌の判定法 |
| JP2017090102A (ja) * | 2015-11-05 | 2017-05-25 | 和光純薬工業株式会社 | 浸潤性乳癌の判定法 |
| WO2019054326A1 (ja) * | 2017-09-13 | 2019-03-21 | 三菱スペース・ソフトウエア株式会社 | コピー数計測装置、コピー数計測プログラム、コピー数計測方法および遺伝子パネル |
| JP2019053395A (ja) * | 2017-09-13 | 2019-04-04 | 三菱スペース・ソフトウエア株式会社 | コピー数計測装置、コピー数計測プログラム、コピー数計測方法および遺伝子パネル |
| JP7072825B2 (ja) | 2017-09-13 | 2022-05-23 | 三菱電機ソフトウエア株式会社 | コピー数計測装置、コピー数計測プログラムおよびコピー数計測方法 |
| JP2023175696A (ja) * | 2019-04-30 | 2023-12-12 | 上▲海▼奕▲譜▼生物科技有限公司 | メチル化修飾に基づく腫瘍マーカーｓｔａｍｐ－ｅｐ９及びその応用 |
| JP2023513039A (ja) * | 2020-01-28 | 2023-03-30 | ジェンキュリクス インク | 特定の遺伝子のＣｐＧメチル化の変化を利用した膀胱癌診断用組成物およびその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20090298054A1 (en) | 2009-12-03 |
| US20110269126A1 (en) | 2011-11-03 |
| EP1769086A2 (en) | 2007-04-04 |
| EP1961827A3 (en) | 2008-09-17 |
| EP2302073A1 (en) | 2011-03-30 |
| EP2281902A1 (en) | 2011-02-09 |
| EP1961827A2 (en) | 2008-08-27 |
| WO2006008128A2 (en) | 2006-01-26 |
| WO2006008128A3 (en) | 2006-07-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2008506407A (ja) | 乳房細胞増殖性疾患を検出するためのエピジェネティックな方法および核酸 | |
| JP5883677B2 (ja) | 前立腺細胞増殖障害の予後に関連する遺伝子発現分析のための方法および核酸 | |
| AU2004237861B2 (en) | Prognostic markers for prediction of treatment response and/or survival of breast cell proliferative disorder patients | |
| US20170283880A1 (en) | Methods and nucleic acids for analyses of colorectal cell proliferative disorders | |
| US9939441B2 (en) | Methods and nucleic acids for analyses for cellular proliferative disorders | |
| US9181587B2 (en) | Methods and nucleic acids for the analysis of gene expression associated with the development of prostate cell proliferative disorders | |
| US20170067119A1 (en) | Methods and nucleic acids for the analysis of gene expression associated with the development of prostate cell proliferative disorders | |
| US20080171318A1 (en) | Epigenetic Methods and Nucleic Acids for the Detection of Lung Cell Proliferative Disorders | |
| WO2005123945A2 (en) | Epigenetic markers for the treatment of breast cancer | |
| US20060024684A1 (en) | Prognostic markers for prediction of treatment response and/or survival of breast cell proliferative disorder patients | |
| US20110171637A1 (en) | Methods and nucleic acids for analyses of cellular proliferative disorders | |
| EP1561821A2 (en) | Prognostic markers for prediction of treatment response and/or survival of breast cell proliferative disorder patients | |
| US20090269736A1 (en) | Prognostic markers for prediction of treatment response and/or survival of breast cell proliferative disorder patients | |
| JP2005224238A (ja) | 乳房細胞増殖障害の患者の治療応答及び／又は生存期間の予測のための予後診断マーカー | |
| WO2007039291A2 (en) | Methods, apparatus and nomograms to determine prostate cancer progression | |
| HK40018204A (en) | Hoxa7 methylation detection reagent | |
| HK40018204B (en) | Hoxa7 methylation detection reagent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080707 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080811 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110328 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110614 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110621 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110725 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110906 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20111122 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20111130 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120329 |