CN112585282A - 鉴定乳腺癌状态的方法和试剂盒 - Google Patents
鉴定乳腺癌状态的方法和试剂盒 Download PDFInfo
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Abstract
一种在受试者中鉴定乳腺癌状态的方法,包括:1)从所述受试者采集生物样品;2)检测所述生物样品中生物标志物基因的甲基化水平,其中所述生物标志物基因选自如下基因的一种或多种:APC、BRCA1、CCND2、CST6、GP5、GSTP1、PITX2、RARB、RASSF1A和SOX17;以及3)将步骤2)检测的甲基化水平与群体中相应生物标志物基因的正常甲基化水平进行比较,以确定所述受试者中的乳腺癌状态。还提供了用于鉴定受试者中乳腺癌状态的试剂盒。
Description
PCT国内申请,说明书已公开。
Claims (38)
- PCT国内申请,权利要求书已公开。
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PCT/CN2018/097296 WO2020019268A1 (zh) | 2018-07-26 | 2018-07-26 | 鉴定乳腺癌状态的方法和试剂盒 |
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EP (1) | EP3828290A4 (zh) |
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Citations (4)
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 |
WO2006008128A2 (en) * | 2004-07-18 | 2006-01-26 | Epigenomics Ag | Epigenetic methods and nucleic acids for the detection of breast cell proliferative disorders |
WO2016168174A1 (en) * | 2015-04-13 | 2016-10-20 | The Translational Genomics Research Institute | Predicting the occurrence of metastatic cancer using epigenomic biomarkers and non-invasive methodologies |
CN107164524A (zh) * | 2017-06-27 | 2017-09-15 | 深圳市优圣康生物科技有限公司 | 用于基因甲基化检测的引物和探针、采样方法、试剂盒 |
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US5541308A (en) * | 1986-11-24 | 1996-07-30 | Gen-Probe Incorporated | Nucleic acid probes for detection and/or quantitation of non-viral organisms |
KR100470221B1 (ko) * | 2002-02-20 | 2005-02-05 | 굿젠 주식회사 | 유전자 프로모터 CpG 아일랜드의 메틸화 여부를분석하는 염기서열분석형 올리고뉴클레오타이드칩, 이의제조방법 및 이를 이용한 암 검색방법 |
WO2008066878A2 (en) * | 2006-11-29 | 2008-06-05 | University Of Vermont And State Agricultural College | Methods and products for diagnosing cancer |
US20070141582A1 (en) * | 2005-12-15 | 2007-06-21 | Weiwei Li | Method and kit for detection of early cancer or pre-cancer using blood and body fluids |
WO2009108917A2 (en) * | 2008-02-29 | 2009-09-03 | Oncomethylome Sciences, S.A. | Markers for improved detection of breast cancer |
CN107922941A (zh) * | 2015-06-15 | 2018-04-17 | 塞弗德公司 | 在自动化反应盒中DNA甲基化的整合的纯化和测量以及突变和/或mRNA表达水平的共同测量 |
-
2018
- 2018-07-26 CN CN201880095981.9A patent/CN112585282A/zh active Pending
- 2018-07-26 EP EP18927940.9A patent/EP3828290A4/en active Pending
- 2018-07-26 US US17/263,306 patent/US20210324479A1/en not_active Abandoned
- 2018-07-26 WO PCT/CN2018/097296 patent/WO2020019268A1/zh active Application Filing
Patent Citations (4)
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 |
WO2006008128A2 (en) * | 2004-07-18 | 2006-01-26 | Epigenomics Ag | Epigenetic methods and nucleic acids for the detection of breast cell proliferative disorders |
WO2016168174A1 (en) * | 2015-04-13 | 2016-10-20 | The Translational Genomics Research Institute | Predicting the occurrence of metastatic cancer using epigenomic biomarkers and non-invasive methodologies |
CN107164524A (zh) * | 2017-06-27 | 2017-09-15 | 深圳市优圣康生物科技有限公司 | 用于基因甲基化检测的引物和探针、采样方法、试剂盒 |
Non-Patent Citations (1)
Title |
---|
符德元: "乳腺癌相关基因异常甲基化的临床实验研究", 《中国博士学位论文全文数据库医药卫生科技辑》 * |
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EP3828290A4 (en) | 2022-03-23 |
US20210324479A1 (en) | 2021-10-21 |
EP3828290A1 (en) | 2021-06-02 |
WO2020019268A1 (zh) | 2020-01-30 |
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