错配修复基因hMLH1甲基化与胃癌的关系  被引量:3

Relationship between mismatch repair gene hMLH1 promoter methylation and gastric carcinoma

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作  者:吴安城[1] 刘希双[1] 杨堃[2] 

机构地区:[1]青岛大学医学院附属医院内镜诊疗中心,山东省青岛市266003 [2]青岛大学医学院附属医院分子生物学实验室,山东省青岛市266003

出  处:《世界华人消化杂志》2008年第13期1407-1411,共5页World Chinese Journal of Digestology

基  金:青岛市科技计划资助项目;No.06-2-2-5-nsh-3~~

摘  要:目的:通过研究散发性胃癌中错配修复基因hMLH1mRNA的表达及其启动子区5'CpG岛甲基化状态,探讨hMLH1基因异常甲基化在胃癌发生过程中的作用.方法:应用甲基化特异性PCR(methylation specific PCR,MSP)检测60例胃癌组织及其癌旁黏膜组织中hMLH1基因启动子区的甲基化状态,逆转录PCR(RT-PCR)检测两种组织中hMLH1mRNA表达情况.结果:胃癌组织hMLH1mRNA表达水平明显低于癌旁组织(t=4.082,P<0.01),hMLH1基因启动子区高甲基化18例(30%),其癌旁黏膜组织中未发现有甲基化.hMLH1基因启动子区甲基化与胃癌的临床病理参数之间无明显的相关性.hMLH1mRNA表达阴性的21例病例中,17例(81%)发生甲基化,而hMLH1mRNA表达阳性的39例中仅有1例(2.5%)发生甲基化,hMLH1mRNA表达降低与甲基化之间存在明显的相关性(χ2=8.0182,P=0.0046).结论:胃癌组织中hMLH1基因启动子区甲基化与其mRNA表达缺失密切相关,是导致hMLH1基因错配修复功能缺陷的重要原因之一.AIM: To detect the hypermethylation status of the 5’CpG island locating in the promoter region of hMLH1 (mismatch repair genes, MMR) gene, and to investigate the role of hMLH1 methylation in gastric carcinogenesis. METHODS: Methylation specific polymerase chain reaction (MS-PCR) was used to examine the methylation status of hMLH1 promoter in 60 gastric carcinomas and 60 caner-adjacent normal tissues, and reverse transcription PCR (RT-PCR) was used to detect the mRNA expression of hMLH1 in the above tissues. RESULTS: The expression of hMLH1 mRNAwas significantly lower in cancer tissues than that in cancer adjacent tissues (t = 4.082, P 〈 0.01). The incidence of hMLH1 promoter methylation occurred in 30% (18/60) cases. No methylation of hMLH1 promoter was found in cancer-adja- cent normal tissues. The methylation of hMLH1 promoter did not correlate with the clinicopathological characteristics of gastric carcinoma. Seventeen of 21 (81%) hMLH1 mRNA-negative cases exhibited prominent methylation, but 1 of 39 (2.5%) hMLH1 mRNA-positive cases showed methylation. There existed a signif icant correlation between hMLH1 methylation and mRNA decrease (χ^2 = 8.0182, P = 0.0046). CONCLUSION: Promoter methylation of hMLH1 is closely related to the expression loss of hMLH1 mRNA, which is involved in gastric carcinogenesis.

关 键 词:胃肿瘤 错配修复基因 甲基化 HMLH1 聚合酶链反应 

分 类 号:R735.2[医药卫生—肿瘤] R394[医药卫生—临床医学]

 

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