胃癌及癌旁组织多个肿瘤相关基因超甲基化

Hypermethylation of multiple tumor-related genes in gastric carcinoma and adjacent normal tissues

目的检测胃癌及癌旁组织肿瘤相关基因超甲基化状态,探讨多个肿瘤相关基因启动子超甲基化与胃癌发生的关系。方法应用甲基化特异性聚合酶链反应,检测23例手术切除的胃癌组织、癌旁组织和10例胃镜活检正常的胃黏膜组织的hMLH1、E-cadherin、GSTP1、p16和p15基因启动子区域的超甲基化状态。结果正常胃黏膜组织未检测到所选基因的超甲基化,22例(95.7%)胃癌组织和7例(30.4%)癌旁组织中检测到超甲基化。在17例(73.9%)胃癌组织和5例(21.7%)癌旁组织可以检测到2个以上基因的超甲基化;E-cadherin、p15和p16三个基因的甲基化率分别为78.3%、82.6%、60.8%,明显高于hMLH1和GSTP1的34.8%和17.4%。结论胃癌组织和邻近的癌旁组织中可以同时检测到多个肿瘤相关基因的甲基化,启动子区域超甲基化导致的基因功能失活可能发生在胃癌肿瘤形成的早期。

Objective To detect the hypermethylation of multiple tumor-related genes in gastric carcinoma tissues and adjacent non- tumor area, and investigate the relationship between methylation in the promoter of multiple tumor-related genes and carcinogenesis of gastric carcinoma. Methods Tumor tissues and their adjacent non-tumor tissues of 23 patients with gastric carcinoma and 10 normal gastric tissues were detected the concurrent CpG-island methylation in 5 tumor-related genes （p15, p16, E-cadherin, GSTP1 and hMLH1） by methylation-specific polymerase chain reaction. Results Hypermethylation was not detected in any normal gastric tissues, but was found in 22 （95.7%） tumor tissues and 7 （30.4%） adjacent non-tumor tissues from the patients with gastric carcinoma. Concurrent methylation in 2 or more tumor-related genes was detected in 17 （73.9%） tumor samples and 5 （21.7%） adjacent gastric tissues. Hypermethylation of E-cadherin （78.3%） , p15 （82.6%） and p16（60.8% ） were more frequently detected than GSTP1 （17.4%） and hM- LH1（34.8% ）. Conclusion The hypermethylation of multiple tumor-related genes is detected frequently in gastric carcinoma and adjacent non-tumor tissues. A mechanism that leads to the dysregulation in CpG-island methylation is likely to be involved in the early gastric carcinogenesis process.