甲基转移酶基因甲基化在结直肠肿瘤中的作用  

The hypermethylation of CpG island in promoter regions and protein expression of O^6-methylguanine-DNA methyltransferase gene in colorectal tumor

作　　者：齐健[1] 朱尤庆[1] 黄梅芳[1] 杨冬[1] 

机构地区：[1]武汉大学中南医院消化内科,430071

出　　处：《中华消化杂志》2004年第10期598-600,共3页Chinese Journal of Digestion

基　　金：2002年湖北省科技攻关计划资助项目(2002AA301C84)

摘　　要：目的探讨6氧甲基鸟嘌呤DNA甲基转移酶(MGMT)基因启动子CpG岛高甲基化在结直肠肿瘤发生、发展中的作用。方法用甲基特异性PCR检测20例正常大肠黏膜、27例散发性结直肠腺瘤和62例散发性结直肠腺癌组织DNA中MGMT基因启动子的甲基化,同时用免疫组化方法检测MGMT蛋白的表达情况。结果正常大肠黏膜组织均未显示甲基化条带,分别有40.7%(11/27)的腺瘤组织和43.5%(27/62)的腺癌组织存在MGMT基因启动子CpG岛高甲基化。正常大肠黏膜胞核和胞质表达MGMT蛋白,22.2%(6/27)的腺瘤和45.2%(28/62)的腺癌MGMT蛋白表达缺失,其差异有显著性(P=0.041)。6例MGMT表达缺失的腺瘤中5例存在甲基化(P=0.027),28例表达缺失的腺癌中24例存在甲基化(P<0.001)。结论结直肠肿瘤中存在高频率MGMT基因启动子高甲基化和蛋白表达缺失,腺癌中蛋白表达缺失比腺瘤中更常见。MGMT蛋白表达缺失与MGMT基因启动子区域高甲基化有关。MGMT基因表型遗传性失活可能在结直肠肿瘤发生过程中起重要作用。Objective To investigate the effect of promoter hypermethylation of O 6 methylguanine DNA methyltransferase (MGMT) gene on colorectal tumorigenesis and progression. Methods The promoter hypermethylation of O 6 methylguanine DNA methyltransferase gene was assayed in 27 sporadic colorectal adenomas, 62 sporadic colorectal carcinomas and 20 normal colorectal mucosa tissues by methylation specific PCR. At the same time, the expression of MGMT protein was studied in the same samples using immunohistochemistry. Results None of the normal colorectal mucosa tissues showed methylated bands. Promoter hypermethylation was detected in 40.7%(11/27) of adenomas and 43.5% (27/62) of carcinomas, respectively. MGMT proteins were expressed in nucleus and cytoplasm of normal colorectal mucosa tissues. Loss of MGMT expression was found in 22.2% (6/27) of adenomas and 45.2% (28/62) of carcinomas, respectively. There were significant difference among them ( P =0.041). Methylation was detected in 5 of the 6 adenomas( P =0.027) and 24 of the 28 carcinomas( P <0.001) with losing MGMT expression.Conclusions Promoter hypermethylation and loss of expression of MGMT gene were common events in colorectal tumorigenesis, and loss of expression of MGMT occurs more frequently in carcinoma than in adenoma in sporadic patients. Loss of MGMT expression was associated with hypermethylation of the CpG island of MGMT gene in colorectal tumor. It suggests that epigenetic inactivation of MGMT plays an important role in colorectal tumorigenesis.

关 键 词：结直肠肿瘤 高甲基化 蛋白表达缺失 MGMT基因 腺瘤 腺癌 大肠黏膜 启动子 CPG岛 表型遗传 

分 类 号：R735.3[医药卫生—肿瘤]