Promoter hypermethylation of tumor-related genes in gastric intestinal metaplasia of patients with and without gastric cancer
Promoter hypermethylation of tumor-related genes in gastric intestinal metaplasia of patients with and without gastric cancer
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DOI：
10.1002/ijc.10783
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发表时间：
2002-12-20
影响因子：
6.4
通讯作者：
Sung, JJY
中科院分区：
文献类型：
--
作者：
To, KF;Leung, WK;Sung, JJY
启动子高甲基化是人类癌症（包括胃癌）基因沉默的另一种机制。虽然肠上皮化生（IM）通常被认为是胃的癌前病变，但我们的研究检查了患有和不患有胃癌的患者肠上皮化生中基因启动子高甲基化的存在。我们检查了 31 个胃癌样本、36 个胃 IM（21 个与胃癌相关，15 个来自非癌症患者）和 10 个正常胃活检组织。从石蜡包埋切片中仔细显微解剖含有 IM 病灶的组织。通过甲基化特异性 PCR 检查亚硫酸氢盐修饰的 DNA 中 DAP 激酶、E-钙粘蛋白、GSTP1、p14、p15、p16、RASSFIA 和 hMLH1 中基因启动子的高甲基化。对照胃组织均未检测到高甲基化，但在胃癌和 IM 中经常检测到基因启动子高甲基化。癌症和 IM 中甲基化基因的平均数量分别为 3.0 和 1.4 (p < 0.0001)。癌症患者 IM 中的甲基化均与相应肿瘤样本中同时发生的甲基化相关。从癌症和非癌症患者获得的 IM 中甲基化基因的数量相似。通过检查这些基因的甲基化模式，发现了 3 种不同的甲基化模式：高甲基化在癌症中比在 IM 中更常见（DAP 激酶、p14、p15 和 p16）；癌症和 IM 中甲基化的频率相当（E-钙粘蛋白和 hMLH1）；并且没有甲基化（GSTP1）。在癌症和非癌症患者的胃IM中经常检测到肿瘤相关基因的异常甲基化，这表明它们早期参与了胃癌发生的多步进展。 (C) 2002 Wiley-Liss, Inc.
Promoter hypermethylation is an alternative mechanism of gene silencing in human cancers including gastric cancer. While intestinal metaplasia (IM) is generally regarded as a precancerous lesion of the stomach, our study examines the presence of gene promoter hypermethylation in IM of patients with and without gastric cancer. We examined 31 samples of gastric cancer, 36 gastric IM (21 associated with gastric cancer and 15 from noncancer patients) and 10 normal gastric biopsies. Tissues containing foci of IM were carefully microdissected from paraffin-embedded section. Bisulfite-modifiedDNA was examined for gene promoter hypermethylation in DAP-kinase, E-cadherin, GSTP1, p14, p15, p16, RASSFIA and hMLH1 by methylation-specific-PCR. None of the control gastric tissues had hypermethylation detected, but gene promoter hypermethylation was frequently detected in gastric cancer and IM. The mean number of methylated genes in cancer and IM was 3.0 and 1.4, respectively (p < 0.0001). Methylation in IM from cancer patients was all associated with concurrent methylation in the corresponding tumor samples. The numbers of methylated genes were similar in IM obtained from cancer and noncancer patients. By examining the methylation patterns of these genes, 3 differential methylation patterns were recognized: hypermethylation was more frequent in cancer than in IM (DAP-kinase, p14, p15 and p16); comparable frequencies of methylation in cancer and IM (E-cadherin and hMLH1); and no methylation (GSTP1). Aberrant methylation in tumor-related genes is frequently detected in gastric IM of both cancer and noncancer patients, suggesting their early involvement in the multistep progression of gastric carcinogenesis. (C) 2002 Wiley-Liss, Inc.