The CpG Island Methylator Phenotype: What's in a Name?
The CpG Island Methylator Phenotype: What's in a Name?
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DOI：
10.1158/0008-5472.can-12-4306
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发表时间：
2013-10-01
期刊：
影响因子：
11.2
通讯作者：
van Engeland, Manon
中科院分区：
文献类型：
--
作者：
Hughes, Laura A. E.;Melotte, Veerle;van Engeland, Manon
尽管CpG岛甲基化表型（CIMP）首先被鉴定并且在结肠直肠癌中被最广泛地研究，但是术语“CIMP”在过去十年中被反复用于描述其他肿瘤类型中的CpG岛启动子甲基化，所述其他肿瘤类型包括膀胱癌、乳腺癌、子宫内膜癌、胃癌、胶质母细胞瘤（胶质瘤）、肝细胞癌、肺癌、卵巢癌、胰腺癌、肾细胞癌和前列腺癌以及白血病。黑色素瘤、十二指肠腺癌、肾上腺皮质癌和神经母细胞瘤。据报道，CIMP可用于预测各种肿瘤类型的预后和治疗反应，但目前尚不清楚CIMP是否是人类肿瘤的普遍现象，或者是否应该有癌症特异性的表型定义。最近，它表明，体细胞异柠檬酸脱氢酶-1（IDH 1）突变，经常在胶质瘤中观察到，建立CIMP在原代人星形胶质细胞通过重塑甲基化。有趣的是，体细胞IDH 1和IDH 2突变，以及与高甲基化表型相关的10 - 11易位（泰特）甲基胞嘧啶双加氧酶-2（TET 2）的功能丧失突变，也分别见于Ollier病和Mafucci综合征以及白血病患者的多发性内生软骨瘤中。这些数据为阐明CIMP的分子基础提供了初步线索。虽然CIMP似乎是一种发生在各种癌症类型中的现象，但其定义不明确，并且对于每种肿瘤都有所不同。目前的观点讨论了CIMP一词在癌症中的使用，其在临床实践中的意义，以及未来的方向，可能有助于确定CIMP在不同形式的人类肿瘤中的真正原因和定义。(c)2013年AACR。
Although the CpG island methylator phenotype (CIMP) was first identified and has been most extensively studied in colorectal cancer, the term "CIMP" has been repeatedly used over the past decade to describe CpG island promoter methylation in other tumor types, including bladder, breast, endometrial, gastric, glioblastoma (gliomas), hepatocellular, lung, ovarian, pancreatic, renal cell, and prostate cancers, as well as for leukemia, melanoma, duodenal adenocarninomas, adrenocortical carcinomas, and neuroblastomas. CIMP has been reported to be useful for predicting prognosis and response to treatment in a variety of tumor types, but it remains unclear whether or not CIMP is a universal phenomenon across human neoplasia or if there should be cancer-specific definitions of the phenotype. Recently, it was shown that somatic isocitrate dehydrogenase-1 (IDH1) mutations, frequently observed in gliomas, establish CIMP in primary human astrocytes by remodeling the methylome. Interestingly, somatic IDH1 and IDH2 mutations, and loss-of-function mutations in ten-eleven translocation (TET) methylcytosine dioxygenase-2 (TET2) associated with a hypermethylation phenotype, are also found in multiple enchondromas of patients with Ollier disease and Mafucci syndrome, and leukemia, respectively. These data provide the first clues for the elucidation of a molecular basis for CIMP. Although CIMP appears as a phenomenon that occurs in various cancer types, the definition is poorly defined and differs for each tumor. The current perspective discusses the use of the term CIMP in cancer, its significance in clinical practice, and future directions that may aid in identifying the true cause and definition of CIMP in different forms of human neoplasia. (c) 2013 AACR.