hMLH1基因高甲基化在胃癌发生、发展中的作用

基因启动子区CpG岛甲基化使许多基因失活，从而导致恶性肿瘤的发生和发展。目的：检测hMLHl基因启动子区CpG岛甲基化水平，探讨其胃癌发生、发展中的作用。方法：以甲基化特异性聚合酶链反应（MSP）检测41例胃癌、40例癌前病变和38例对照组织中hMLHl基因启动子区CpG岛甲基化状态，并分析其与胃癌患者临床病理特征的关系。结果：胃癌组织中hMLHl基因启动子区CpG岛甲基化阳性率为34．1％，显著高于癌前病变组的5．0％和对照组的0％（P〈0．05）。hMLHl基因甲基化阳性率与胃癌患者的年龄和肿瘤浸润深度有关（阳性率分别为46．4％对7．7％和55．0％对14.3％，P〈0．05），与性别、肿瘤分化程度和淋巴结转移无关（阳性率分别为34．8％对33．3％、28．0％对43．8％和38．1％对30．0％）。结论：胃癌组织中存在hMLHl基因启动子区CpG岛高甲基化，可能与胃癌的发生、发展有关．且可能在老年胃癌患者的肿瘤发生过程中起重要作用。

Role of hMLH1 Gene Hypermethylation in the Development and Progression of Gastric Cancer

Background： The CpG island methylation in gene promoter causes the inactivation of many genes, thereby inducing the development and progression of malignant tumor. Aims To explore the role of CpG island methylation in hMLH 1 gene promoter in the development and progression of gastric cancer. Methods： Methylation-specific polymerase chain reaction （MSP） was used to detect the CpG island methylation in hMLH1 gene promoter in 41 specimens of gastric cancer, 40 specimens of premalignant lesions and 38 specimens of normal controls. The relationship between the CpG island methylation and clinicopathologic characteristics was analyzed. Results： The positivity rate of the CpG island methylation in hMLH1 gene promoter was significantly higher in gastric cancer than that in premalignant lesions and normal controls （34.1% vs. 5.0% and 0%, P〈0.05）. The positivity rate of hMLH1 gene methylation was related with age and depth of tumor infiltration （positivity rate： 46.4% vs. 7.7% and 55.0% vs. 14.3%, P〈0.05）, but not related with gender, tumor differentiation and lymph node metastasis （positivity rate： 34.8% vs. 33.3%, 28.0% vs. 43.8% and 38.1% vs. 30.0%）. Conclusions： The CpG island hypermethylation in hMLH1 gene promoter exists in gastric cancer, which may be involved in the development and progression of gastric cancer, and may play an important role in the development of gastric cancer in aged patients.