DNA修复因子MGMT甲基化与子宫颈癌的相关性研究

RELATIONSHIP BETWEEN HYPERMETHYLATION OF DNA REPAIR GENE MGMT AND CERVICAL CARCINOMA

目的探讨O6-甲基鸟嘌呤-DNA甲基转移酶(O6-methylguanine-DNA methyl-transferase,MGMT)基因启动子区甲基化状态与子宫颈癌的相关关系。方法采用甲基化特异性聚合酶链反应(methylation-specific PCR,MSP)分析子宫颈癌组织中MGMT基因启动子区甲基化状态,结合定量PCR(RT-PCR)检测MGMT mRNA表达情况行综合分析。结果宫颈癌组织中MG-MT基因启动子甲基化率达71.15%(37/52),而非癌对照组织中均无甲基化。不同临床分期的宫颈癌组织MGMT甲基化率也各不相同(P<0.01),组织分化程度越低,MGMT甲基化率越高(P<0.05)。37例甲基化的癌组织中有MGMTmRNA表达,不同临床分期和不同组织分化程度的MGMT mRNA表达量差异均有统计学显著性(P<0.01)。结论 DNA修复因子MGMT甲基化影响其mRNA的表达,可能与子宫颈癌的发生存在联系。

Objective To explore the correlations between hypermethylation status in the promoter region of O^6-methylguanine DNA methyltransferase（MGMT）gene and carcinogenesis of cervical cancer.Methods Methylation specific polymerase chain reaction（MSP）was used to detect the CpG island methylation status in the promoter region of MGMT gene in 52 specimens of cervical cancer and 30 non-cancerous tissues.Relative quantitative PCR method was used to determine the expression of MGMT mRNA in these tissues.Results Promoter hypermethylation of MGMT gene was found in 37 specimens of cervical cancer（37/52,71.15%）and not detected in all of the control group.The status of promoter hypermethylation of MGMT gene and the expression of MGMT mRNA in tumor tissues were significant difference（P〈0.05） in different clinical stages of cervical cancer and different degree of differentiated cervical cancer.Conclusion The results show that the hypermethylation of promoter region of MGMT gene affects the expression of MGMT mRNA in cervical cancer tissues.It possibly plays a key role in carcinogenesis of cervical cancer.