Concordant CpG island methylation in hyperplastic polyposis
Concordant CpG island methylation in hyperplastic polyposis
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DOI：
10.1016/s0002-9440(10)64872-9
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发表时间：
2002-02-01
影响因子：
6
通讯作者：
Rashid, A
中科院分区：
文献类型：
--
作者：
Chan, AOO;Issa, JPJ;Rashid, A
CpG岛甲基化表型(CIMP)是一种新发现的以多个CpG岛甲基化为特征的结直肠癌和腺瘤的致癌机制。CIMP的病因尚不清楚。我们研究了CIMP在增生性息肉(HPS)中的作用，重点是多发性HPS(5-10 HPS)、大型HPS(1 Cm)或增生性息肉(>；20 HPS)的患者。应用甲基化特异性聚合酶链式反应分析了17例HPS中102例HPS、8例锯齿状腺瘤、19例管状腺瘤和9例腺癌中p16、MINT1、MINT2、MINT31和hMLH1的甲基化状态，并分析了14例散发性HPS中的16例散发性HPS。散发性Hp均为CIMP阴性(无甲基化)，但43%的多发性/大型Hp或增生性息肉的Hp为CIMP高表达(两个或两个以上甲基化，P=0.00001)。四个基因座之间的甲基化在HPS内相关(优势比，3.41；P=0.002)，同一患者内HPS的甲基化状态也相关(优势比，5.92；P=0.0001)。CIMP高表达主要见于右半结肠和/或锯齿状腺瘤(P=0.0009)，且与K-ras原癌基因突变阴性有关(优势比5.08；P=0.0 3)。我们在多发性/大型HPS或增生性息肉病中HPS的一致性CpG岛甲基化的发现支持这样的概念，即一些患者具有以多发性HPS和其他结直肠病变的甲基化为特征的高甲基化表型。高甲基化子表型与患者特定的因素有关，例如致癌暴露或遗传易感性。
The CpG island methylator phenotype (CIMP) is a newly described mechanism for carcinogenesis in colorectal carcinomas and adenomas characterized by methylation of multiple CpG islands. The causes of CIMP are unknown. We studied CIMP in hyperplastic polyps (HPs), with emphasis on patients with multiple HPs (5 to 10 HPs), large HPs (one HP >1 cm) or hyperplastic polyposis (>20 HPs). Methylation of p16, MINT1, MINT2, MINT31, and hMLH1 was analyzed by methylation-specific polymerase chain reaction in 102 HPs, 8 serrated adenomas, 19 tubular adenomas, and 9 adenocarcinomas from 17 patients, with multiple/large HPs or hyperplastic polyposis and in 16 sporadic HPs from 14 additional patients. Sporadic HPs were CIMP-negative (not methylated at any locus), but 43% of HPs from multiple/large HPs, or hyperplastic polyposis were CIMP-high (two or more methylated loci, P = 0.00001). Methylation among the four loci was correlated within HPs (odds ratio, 3.41; P = 0.002), and the methylation status of HPs within the same patient was also correlated (odds ratio, 5.92; P = 0.0001). CIMP-high HPs were present primarily in patients with a predominance of HPs in the right colon and/or serrated adenomas (P = 0.0009) and were associated with the absence of K-ras proto-oncogene mutations (odds ratio, 5.08; P = 0.03). Our findings of concordant CpG island methylation of HPs in multiple/large HPs or hyperplastic polyposis supports the concept that some patients have a hypermethylator phenotype characterized by methylation of multiple HPs and other colorectal lesions. The hypermethylator phenotype is related to patient-specific factors, such as carcinogenic exposure or genetic predisposition.