EA034232B1 - Способы и нуклеиновые кислоты для определения прогноза у больных раком - Google Patents
Способы и нуклеиновые кислоты для определения прогноза у больных раком Download PDFInfo
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- EA034232B1 EA034232B1 EA201400117A EA201400117A EA034232B1 EA 034232 B1 EA034232 B1 EA 034232B1 EA 201400117 A EA201400117 A EA 201400117A EA 201400117 A EA201400117 A EA 201400117A EA 034232 B1 EA034232 B1 EA 034232B1
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- 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
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- C12Q2600/00—Oligonucleotides characterized by their use
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- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
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- 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
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| US10706957B2 (en) | 2012-09-20 | 2020-07-07 | The Chinese University Of Hong Kong | Non-invasive determination of methylome of tumor from plasma |
| 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 |
| NZ727493A (en) * | 2014-06-04 | 2023-07-28 | Quest Diagnostics Invest Llc | Methylated markers for colorectal cancer |
| CN104745575B (zh) | 2014-08-08 | 2019-03-12 | 博诚研究中心 | 用于检测细胞增殖性异常或疾病程度分级的基因组合物及其用途 |
| ES3017068T3 (en) | 2014-12-31 | 2025-05-12 | Guardant Health Inc | Detection and treatment of disease exhibiting disease cell heterogeneity and systems and methods for communicating test results |
| CN115181802A (zh) * | 2015-04-23 | 2022-10-14 | 博尔诚（北京）科技有限公司 | 一种检测Septin9基因甲基化的试剂盒及其应用 |
| WO2017009322A1 (en) * | 2015-07-15 | 2017-01-19 | Universiteit Gent | Probes and a methylation in situ hybridization assay |
| JP6897970B2 (ja) * | 2015-09-08 | 2021-07-07 | 国立大学法人山口大学 | 大腸腫瘍の有無を検査する方法 |
| WO2018031760A1 (en) | 2016-08-10 | 2018-02-15 | Grail, Inc. | Methods of preparing dual-indexed dna libraries for bisulfite conversion sequencing |
| SG10202111266VA (en) | 2017-04-19 | 2021-11-29 | Singlera Genomics Inc | Compositions and methods for library construction and sequence analysis |
| CN107385056A (zh) * | 2017-08-10 | 2017-11-24 | 上海时代基因医学科技有限公司 | 一种检测SEPT9基因不同Cpg岛甲基化的试剂盒及应用 |
| WO2019076949A1 (en) * | 2017-10-18 | 2019-04-25 | Deutsches Krebsforschungszentrum | MEANS AND METHODS FOR CLASSIFYING COLORECTAL CANCERS |
| EP3717502B1 (en) * | 2017-11-29 | 2025-04-23 | The Regents of The University of Michigan | Compositions and methods for characterizing cancer |
| CN108796080B (zh) * | 2018-06-06 | 2022-06-07 | 苏州唯善生物科技有限公司 | 用于结直肠癌诊断、检测或筛查的引物和探针组 |
| CN109055552A (zh) * | 2018-08-23 | 2018-12-21 | 北京迈基诺基因科技股份有限公司 | 检测Septin9基因启动子是否甲基化的方法及其专用成套试剂 |
| CN112195243A (zh) * | 2020-09-22 | 2021-01-08 | 北京华大吉比爱生物技术有限公司 | 一种检测多基因甲基化的试剂盒及其应用 |
| KR102404750B1 (ko) * | 2021-10-14 | 2022-06-07 | 주식회사 엔도믹스 | 세포 유리 dna를 이용한 대장암 진단을 위한 메틸화 마커 유전자 및 이의 용도 |
| CN114561452A (zh) * | 2022-03-10 | 2022-05-31 | 天津市人民医院 | mSEPT9作为预测结直肠癌患者术后复发风险标志物及用于评价化疗方案有效性的应用 |
| KR102559496B1 (ko) * | 2022-04-26 | 2023-07-25 | 연세대학교 산학협력단 | 핵산의 메틸화 여부 확인용 조성물 및 핵산의 메틸화 여부를 확인하는 방법 |
| CN115248313A (zh) * | 2022-08-03 | 2022-10-28 | 中山市人民医院 | 肠癌外周血免疫细胞m5C标志物的应用 |
| CN115029462B (zh) * | 2022-08-10 | 2022-11-08 | 中国农业科学院农业质量标准与检测技术研究所 | 一种动植物疫病的核酸标准物质、形貌模拟方法及其应用 |
| WO2024064369A1 (en) * | 2022-09-23 | 2024-03-28 | Flagship Pioneering Innovations Vi, Llc | Methods for amplifying nucleic acids |
| WO2024107441A1 (en) * | 2022-11-14 | 2024-05-23 | Trustees Of Dartmouth College | Systemic biomarkers for the dynamic assessment of tumor burden and treatment efficacy in high grade gliomas |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005040421A2 (en) * | 2003-10-17 | 2005-05-06 | Martin Widschwendter | Prognostic and diagnostic markers for cell proliferative disorders of the breast tissues |
| WO2007118704A2 (en) * | 2006-04-17 | 2007-10-25 | Epigenomics Ag | Methods and nucleic acids for the detection of colorectal cell proliferative disorders |
| WO2008009479A1 (en) * | 2006-07-21 | 2008-01-24 | Epigenomics Ag | Methods and nucleic acids for analyses for cellular proliferative disorders |
| US20100143929A1 (en) * | 2008-12-04 | 2010-06-10 | Rush University Medical Center | Dna methylation based test for monitoring efficacy of treatment |
| US20110027789A1 (en) * | 2009-08-03 | 2011-02-03 | Epigenomics Ag | Methods for preservation of genomic dna sequence complexity |
| US20110039719A1 (en) * | 2005-04-15 | 2011-02-17 | Epigenomics Ag | Methods and nucleic acids for the analyses of cellular proliferative disorders |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US412900A (en) | 1889-10-15 | roaers | ||
| US150000A (en) | 1874-04-21 | Improvement in cigar mouth - pieces | ||
| 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 |
| AU1061395A (en) | 1993-11-30 | 1995-06-19 | Mcgill University | Inhibition of dna methyltransferase |
| 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 |
| CN1150317C (zh) * | 1999-08-10 | 2004-05-19 | 中国医学科学院肿瘤医院肿瘤研究所 | 一种食管癌相关新基因 |
| US6858388B2 (en) * | 2000-09-20 | 2005-02-22 | Case Western Reserve University | Methods and compositions for detecting cancers associated with methylation of hMLH1 promoter DNA |
| 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 |
| CN1187456C (zh) * | 2001-11-27 | 2005-02-02 | 暨南大学 | CpG岛甲基化检测试剂盒及其应用 |
| CA2549852A1 (en) | 2003-12-11 | 2005-06-30 | Epigenomics Ag | Method and nucleic acids for the improved treatment of breast cell proliferative disorders |
| JP4765058B2 (ja) | 2004-12-13 | 2011-09-07 | 国立大学法人 岡山大学 | 核酸修飾前の検体の前処理方法 |
| WO2007085497A2 (en) | 2006-01-30 | 2007-08-02 | Epigenomics Ag | Markers for the prediction of outcome of anthracycline treatment |
| JP2010517582A (ja) * | 2007-02-12 | 2010-05-27 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 結腸癌の早期検出および予後診断の方法 |
| JP5378687B2 (ja) | 2007-03-02 | 2013-12-25 | エフ．ホフマン−ラ ロシュ アーゲー | Ｂａｓｐ１遺伝子および／またはｓｒｄ５ａ２遺伝子中のメチル化シトシンを利用する、肝臓癌、肝臓癌発症リスク、肝臓癌再発リスク、肝臓癌悪性度および肝臓癌の経時的進展の検出方法 |
| US20110177511A1 (en) * | 2008-09-19 | 2011-07-21 | Noriaki Yamamoto | Method for determining breast cancer metastasis and method for evaluating serum |
-
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005040421A2 (en) * | 2003-10-17 | 2005-05-06 | Martin Widschwendter | Prognostic and diagnostic markers for cell proliferative disorders of the breast tissues |
| US20110039719A1 (en) * | 2005-04-15 | 2011-02-17 | Epigenomics Ag | Methods and nucleic acids for the analyses of cellular proliferative disorders |
| WO2007118704A2 (en) * | 2006-04-17 | 2007-10-25 | Epigenomics Ag | Methods and nucleic acids for the detection of colorectal cell proliferative disorders |
| WO2008009479A1 (en) * | 2006-07-21 | 2008-01-24 | Epigenomics Ag | Methods and nucleic acids for analyses for cellular proliferative disorders |
| US20100143929A1 (en) * | 2008-12-04 | 2010-06-10 | Rush University Medical Center | Dna methylation based test for monitoring efficacy of treatment |
| US20110027789A1 (en) * | 2009-08-03 | 2011-02-03 | Epigenomics Ag | Methods for preservation of genomic dna sequence complexity |
Non-Patent Citations (3)
| Title |
|---|
| DEVOS Theo et al. Circulating Methylated SEPT9 DNA in Plasma Is a Biomarker for colorectal Cancer., Clinical Chemistry, v. 55, n. 7, p. 1337-1346, с. 1337-1342, фиг. 2, табл. 2 * |
| HOFFMANN Andreas-Claudius et al. Methylated DAPK and APC promoter DNA detection in peripheral blood is significantly associated with apparent residual tumor and outcome. J Cancer Res Clin Oncol, 2009, v. 135, n. 9, p. 1231-1237, с. 1232-1235, табл. 2 * |
| KOLLERMANN JENS; KEMPKENSTEFFEN CARSTEN; HELPAP BURKHARD; SCHRADER MARK; KRAUSE HANS; MULLER MARKUS; MILLER KURT; SCHOSTAK MARTIN: "Impact of hormonal therapy on the detection of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) in prostate cancer", BMC UROLOGY, BIOMED CENTRAL, LONDON, GB, vol. 6, no. 1, 27 June 2006 (2006-06-27), GB, pages 15, XP021016943, ISSN: 1471-2490, DOI: 10.1186/1471-2490-6-15 * |
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