脑胶质瘤患者组织和血清MGMT、hMLH1和hMSH2基因启动子甲基化状态检测

目的探讨脑胶质瘤患者组织和血清中MGMT、hMLH1和hMSH2基因启动子CpG岛甲基化发生率及相关性。方法甲基化特异性PCR（MSP）检测39例脑胶质瘤组织样本及32例预处理的脑胶质瘤血清样本中MGMT、hMLH1和hMSH2基因启动子区的甲基化状态。结果脑胶质瘤组织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％，肿瘤组织中至少有一种基因甲基化的发生率为64．1％（25／39）；在脑胶质瘤患者外周循环血液中检测到了相关基因甲基化系列，并且与组织中基因甲基化发生率明显相关。结论MGMT、hMLH1和hMSH2基因启动子甲基化是脑胶质瘤发生过程中常见的分子事件，血清中相关基因DNA甲基化检测有可能为脑胶质瘤诊断和个体化化疗提供一种稳定的无创性检测指标。

Detection of Hypermethylated MGMT,hMLH1 and hMSH2 Genes in Tumor and Serum DNA of Gliomas Patients

Objective This study is aimed to investigate the prevalence of promoter CpG island methylation of O^6-methylguananine-DNA methyhransferase （ MGMT）, mismatch repair genes （ hM- LH1 and hMSH2 ） in both tumor and serum samples of gliomas. Methods Methylation-specific PCR （MSP） was employed to detect promoter CpG island,methylation of MGMT, hMLH1 as well as hMSH2 gene in 39 samples of surgical tumor tissues and 32 samples of pretreatment serum from gliomas patients. Results Promoter CpG island methylation,ofMGMT, hMLH1 and hMSH2 was detected in 46. 2 % , 10. 3 % and 20. 5 % of gliomas tumor. DNA and 40. 6 % , 9.4 % and 18.8 % of serum DNA respectively. Of three genes, at least one gene was detectable for mythylation in 64. 1% （25/39） of tumor and in 59.4 % （19/32） of serum. In 21 g lioma patients, while MGMT, hMLH1 and hMSH2 genes were found to be methylated in tumor samples, the hypermythylation of the genes was correspondingly detected in serum sampies, with the level of 77.7 % （7/9）, 66. 7 % （2/3）and 75 % （3/4） respectively. Conclusions Methylation of promoter CpG island may be a frequent event in gliomas carcinogenesis. Detection of methylation of MGMT, hMLH1 and hMSH2 in serum sample may be used as diagnostic method beneficial for gliomas treatment.