大肠癌组织微卫星不稳与hMLH1和hMSH2基因启动子区甲基化状态  

Methylation of hMLH1 and hMSH2 promoter in colorectal cancer with microsatellite instability

作　　者：房殿春[1] 杨仕明[1] 杨建民[1] 刘海峰[1] 彭贵勇[1] 肖天利[1] 汪荣泉[1] 刘为纹[1] 

机构地区：[1]中国人民解放军第三军医大学西南医院全军消化专科中心,重庆市400038

出　　处：《世界华人消化杂志》2003年第3期302-305,共4页World Chinese Journal of Digestology

摘　　要：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.AIM:To explore methylation of hMLH1 and hMSH2 promoter with microsatellite instability (MSI) in colorectal carcinomas. METHODS:Methylation of hMLH1 and hMSH2 promoter was measured with methylation-specific PCR;MSI was analyzed by PCR-based methods. RESULTS:No methylation of hMLH1 and hMSH2 promoter was found in 10 normal colorectal mucosas. Seventy-six cases of sporadic colorectal carcinoma were studied for methylation of hMLH1 and hMSH2 promoter and MSI. Methylation of hMLH1 promoter was detected in 8 (10.5 %) colorectal carcinomas and none in hMSH2. Frequence of hMLH1 methylation on right-sided colorectal cancer (23.1 %) was significantly higher than that on left one (4.0 %, P <0.05). MSI was detected in at least one locus in 26.3 %( 20/76) of the tumors analyzed with five microsatellite markers. Frequence of hMLH1 methylation in gastric cancer with MSI-H (80.0 %)was significantly higher than that in gastric cancer with MSI-L (20.0 %, P <0.01) and with MSS (10.7 %, P <0.001). CONCLUSION:Methylation of hMLH1 promoter is related to right-sided colorectal cancer and involved in the MSI pathway.

关 键 词：大肠癌 微卫星不稳 HMLH1 HMSH2 基因启动 子区 甲基化状态 

分 类 号：R735.34[医药卫生—肿瘤]