DNA 甲基化异常将结直肠癌划分为具有临床显著差异的亚群，并为表观遗传学治疗提供了新的靶点。
DNA methylation aberrancies delineate clinically distinct subsets of colorectal cancer and provide novel targets for epigenetic therapies.
机构信息
Department of Biochemistry and Molecular Medicine, University of Southern California, USC Norris Comprehensive Cancer Center, Los Angeles, CA USA.
Department of Urology, University of Southern California, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
出版信息
Oncogene. 2018 Feb 1;37(5):566-577. doi: 10.1038/onc.2017.374. Epub 2017 Oct 9.
Abstract
Colorectal cancer (CRC) is a worldwide health concern with respect to both incidence and mortality, and as a result, CRC tumorigenesis, progression and metastasis have been heavily studied, especially with respect to identifying genetic, epigenetic, transcriptomic and proteomic profiles of disease. DNA methylation alterations are hallmarks of CRC, and epigenetic driver genes have been identified that are thought to be involved in early stages of tumorigenesis. Moreover, distinct CRC patient subgroups are organized based on DNA methylation profiles. CRC tumors displaying CpG island methylator phenotypes (CIMPs), defined as DNA hypermethylation at specific CpG islands in subsets of tumors, show high concordance with specific genetic alterations, disease risk factors and patient outcome. This review details the DNA methylation alterations in CRC, the significance of CIMP status, the development of treatments based on specific molecular profiles and the application of epigenetic therapies for CRC patient treatment.
摘要
结直肠癌（CRC）在发病率和死亡率方面都是一个全球性的健康问题，因此，CRC 的发生、发展和转移已被广泛研究，尤其是在确定疾病的遗传、表观遗传、转录组和蛋白质组特征方面。DNA 甲基化改变是 CRC 的标志，已经确定了一些表观遗传驱动基因，这些基因被认为参与了肿瘤发生的早期阶段。此外，还根据 DNA 甲基化谱对不同的 CRC 患者亚组进行了分类。表现出 CpG 岛甲基化表型（CIMP）的 CRC 肿瘤，定义为肿瘤亚群中特定 CpG 岛上的 DNA 高甲基化，与特定的遗传改变、疾病危险因素和患者预后具有高度一致性。本综述详细介绍了 CRC 中的 DNA 甲基化改变、CIMP 状态的意义、基于特定分子谱的治疗方法的发展以及 CRC 患者治疗的表观遗传治疗应用。
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本文引用的文献
1
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Br J Cancer. 2017 Jul 25;117(3):315-321. doi: 10.1038/bjc.2017.178. Epub 2017 Jun 20.
2
TET-mediated active DNA demethylation: mechanism, function and beyond.TET 介导的活性 DNA 去甲基化：机制、功能及其他。
Nat Rev Genet. 2017 Sep;18(9):517-534. doi: 10.1038/nrg.2017.33. Epub 2017 May 30.
3
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Oncotarget. 2017 Mar 7;8(10):17164-17190. doi: 10.18632/oncotarget.15211.
4
Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/stand up 2 cancer study.皮下注射5-氮杂胞苷和恩替诺特联合用于转移性结直肠癌（mCRC）的表观遗传疗法：一项2期联合/站起来对抗癌症研究。
Oncotarget. 2017 May 23;8(21):35326-35338. doi: 10.18632/oncotarget.15108.
5
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6
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J Cancer. 2016 Oct 8;7(14):1984-2004. doi: 10.7150/jca.16244. eCollection 2016.
8
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9
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10
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