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目的:探讨脑胶质瘤患者O6-甲基鸟嘌呤-DNA甲基转移酶基因MGMT和错配修复基因hMLH1、hMSH2启动子CpG岛甲基化状态,及其在烷化剂化疗中的意义。方法:采用甲基化特异性PCR(MSP)方法检测39例脑胶质瘤和6例正常脑组织MGMT、hMLH1和hMSH2基因启动子区的甲基化状态,免疫组化方法测定蛋白表达。结果:脑胶质瘤患者组织MGMT、hMLH1和hMSH2基因启动子区甲基化发生率分别为46.2%、10.3%和20.5%,3种基因启动子未甲基化模式与其对应蛋白表达模式相似,并与患者性别、年龄、病理类型和病理分级无明显相关性。回顾性分析患者资料,显示39例脑胶质瘤患者中,MGMT基因甲基化的患者生存期显著高于MGMT基因未甲基化患者(P<0.05,Log-rank检验)。结论:MGMT及错配修复基因甲基化是脑胶质瘤发生过程中常见的分子事件,可能与肿瘤的发生有关;检测MGMT、hMLH1和hMSH2基因启动子甲基化状态,在判断脑胶质瘤患者预后和预测烷化剂化疗耐药性中可能具有重要意义。
Objective: To investigate the methylation status of CpG islands of O6-methylguanine-DNA methyltransferase gene and mismatch repair gene hMLH1 and hMSH2 promoter in glioma patients and its significance in alkylating agent chemotherapy. Methods: The methylation status of MGMT, hMLH1 and hMSH2 gene promoter in 39 gliomas and 6 normal brain tissues was detected by methylation-specific PCR (MSP). The protein expression was determined by immunohistochemistry. Results: The methylation rates of MGMT, hMLH1 and hMSH2 genes in glioma tissues were 46.2%, 10.3% and 20.5%, respectively. The unmethylation patterns of three gene promoters were similar to their corresponding protein expression patterns, There was no significant correlation between the patients’ gender, age, pathological type and pathological grade. Retrospective analysis of patient data showed that the survival of patients with MGMT methylation was significantly higher than that of MGMT unmethylated patients (P <0.05, Log-rank test) in 39 patients with glioma. Conclusion: Methylation of MGMT and mismatch repair genes is a common molecular event in the process of glioma, which may be related to the tumorigenesis. The methylation status of MGMT, hMLH1 and hMSH2 gene promoters may be detected. Tumor patient prognosis and predict alkylating agent chemotherapy resistance may have important significance.