CpG Island Methylator Phenotype in Cancer
CpG Island Methylator Phenotype in Cancer
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DOI：
10.1002/9780470015902.a0026338
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发表时间：
2017-01
期刊：
影响因子：
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通讯作者：
J. H. Kim;J. Bae;G. Kang
中科院分区：
文献类型：
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作者：
J. H. Kim;J. Bae;G. Kang
异常脱氧核糖核酸(DNA)甲基化是多种癌症的重要表观遗传学改变。在癌变过程中，DNA甲基化优先发生在启动子CpG岛上，在正常细胞中通常不会发生DNA甲基化。启动子CpG岛甲基化导致相应基因转录沉默，因此被认为是肿瘤抑制基因失活的机制之一。在人类癌症中，以广泛的启动子CpG岛超甲基化为特征的独特的分子表型被称为CpG岛甲基化表型(CIMP)。尽管在某些类型的恶性肿瘤中发现了CIMP特有的临床病理和分子相关性，但对于CIMP的诊断标准缺乏共识，而且CIMP在癌症中的预后/预测价值也存在争议。关键概念DNA甲基化异常是癌症的分子标志之一。CpG岛甲基化表型(CIMP)是一种以广泛的启动子CpG岛甲基化为特征的癌症亚型。CIMP在结直肠癌、胃癌和脑胶质瘤中具有代表性。CIMP+结直肠癌与锯齿状瘤变途径有关，预后较差，但CIMP的预测价值仍存在争议。CIMP+胃癌与EB病毒(EBV)阳性和/或微卫星不稳定高(MSI-H)状态相关。CIMP+胶质瘤与异柠檬酸脱氢酶(IDH)突变有关。关键词：表观遗传学；DNA甲基化；CpG岛甲基化表型；结直肠癌；胃癌；胶质瘤
Aberrant deoxyribonucleic acid (DNA) methylation is an important epigenetic change in various cancers. During carcinogenesis, DNA methylation preferentially occurs in promoter CpG islands, which do not usually undergo DNA methylation in normal cells. Promoter CpG island methylation causes transcriptional silencing of the corresponding gene and is thus regarded as one of the mechanisms of tumour suppressor gene inactivation. In human cancers, the unique molecular phenotype characterised by extensive promoter CpG islands hypermethylation has been referred to as the CpG island methylator phenotype (CIMP). Although characteristic clinicopathological and molecular associations of CIMP have been identified in some types of malignancies, there has been a lack of consensus regarding the diagnostic criteria for CIMP, and prognostic/predictive values of CIMP in cancers have been controversial. Key Concepts Aberrant DNA methylation is one of the molecular hallmarks of cancers. The CpG island methylator phenotype (CIMP) indicates a subtype of cancer characterised by widespread promoter CpG islands methylation. CIMP has been identified representatively in colorectal cancers, gastric cancers and brain gliomas. CIMP+ colorectal cancers are associated with the serrated neoplasia pathway and poor prognosis, but the predictive value of CIMP remains controversial. CIMP+ gastric cancers are associated with Epstein–Barr virus (EBV) positivity and/or microsatellite instability-high (MSI-H) status. CIMP+ gliomas are associated with isocitrate dehydrogenase (IDH) mutations. Keywords: epigenetics; DNA methylation; CpG island methylator phenotype; colorectal cancer; gastric cancer; glioma