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目的:探讨大肠癌组织微卫星DNA不稳与hMLH1和hMSH2基因启动子区甲基化状态的关系.方法:采用PCR为基础的方法检测微卫星DNA不稳;采用甲基化特异性PCR方法检测hMLH1和hMSH2基因启动子区的甲基化状态.结果:正常大肠黏膜未见hMLH1和hMSH2基因启动子区的高甲基化.76例大肠癌中检出hMLH1高甲基化8例,占10.5%,而且均为去甲基化和高甲基化并存,未见有hMSH2高甲基化者.检出MSI20例,检出率为26.3%.将MSI分为高频率MSI(MSI-H,≥2个位点)10例、低频率MSI(MSI-L),仅为1个位点10例和MSI阴性(MSS)56例三组,结果右侧大肠癌hMLH1高甲基化检出率(23.1%)显著高于左侧大肠癌(4.0%,P<0.05).MSI-H组hMLH1高甲基化的检出率(8/10)显著高于MSI-L(2/10)和MSS组(6/56,P<0.01-0.001).结论:hMLH1高甲基化与右侧大肠癌的发生有关,可能参与了MSI病理途径,而hMSH2甲基化状态可能与MSI途径无关.
Objective: To investigate the relationship between microsatellite DNA instability and methylation status of hMLH1 and hMSH2 promoter region in colorectal cancer tissue.Methods: The PCR-based method was used to detect microsatellite DNA instability. Methylation-specific PCR hMLH1 and hMSH2 gene promoter region methylation status.Results: Normal colorectal mucosa hMLH1 and hMSH2 gene promoter hypermethylation.High methylation of hMLH1 in 76 cases of colorectal cancer detected in 8 cases, accounting for 10.5%, and both For the co-existence of demethylation and hypermethylation, no hypermethylation of hMSH2 was detected, MSI was detected in 20 cases and the detection rate was 26.3%. MSI was divided into high frequency MSI (MSI-H, ≥2 sites) in 10 cases , Low frequency MSI (MSI-L), only 1 locus in 10 cases and MSI negative (MSS) in 56 cases. The positive rate of hMLH1 hypermethylation (23.1%) in right colorectal cancer was significantly higher than that in left colorectal (4.0%, P <0.05) .The detection rate of hMLH1 hypermethylation in MSI-H group was significantly higher than that in MSI-L (2/10) and MSS group (6/56, P <0.01-0.001 ) .Conclusion: HMLH1 hypermethylation is associated with the development of right colorectal cancer and may be involved in the pathogenesis of MSI. The methylation status of hMSH2 may not be related to MSI.