结、直肠癌中MGMT基因多位点甲基化的定量分析  

The quantitative analysis to evaluate methylation status of 5′-CpG island of MGMT gene in colorectal carcinomas

作　　者：乔颖娟[1] 张定东[2] 孟凡青[3] 王建华[1] 何杰[1] 

机构地区：[1]东南大学附属中大医院病理科,江苏南京210009 [2]东南大学吴健雄实验室,江苏南京210096 [3]南京市鼓楼医院病理科,江苏南京210008

出　　处：《现代医学》2006年第4期223-228,共6页Modern Medical Journal

摘　　要：目的探讨O6-甲基鸟嘌呤-DNA甲基转移酶(O6-m ethylguan ine-DNA m ethyltransferase,MGMT)基因不同位点的甲基化与结、直肠癌发生、进展的关系。方法应用DNA微阵列技术对20例结、直肠癌标本及癌旁组织进行MGMT基因启动子区5种高甲基化模式的定量检测分析。结果20例样本中有17例无论是肿瘤组织还是癌旁组织其各位点均有不同程度的甲基化,且肿瘤组织启动子区各CpG位点甲基化水平均高于其对应的癌旁组织(P<0.05),其中CpG13-15、20-23位点甲基化水平明显增高。MGMT基因各CpG位点的甲基化水平在不同的病理分级和肿瘤淋巴结转移中差异无显著性(均P>0.05)。结论结、直肠癌中存在高频MGMT基因启动子高甲基化,且其甲基化模式不止一种。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。MGMT基因启动子的异常甲基化与肿瘤发展水平并无直接相关性。Objective To explore the effect of hypermethylation of multiple site of 5＇-CpG islands in the promoter regions of O^6-methylguanine-DNA methyltransferase （MGMT） genes on colorectal tumorigenesis and progression. Methods Use a methylation-specific oligonucleotide microarray for quantitative analysis in 20 colorectal carcinomas samples and tissues adjacent to the tumor for hypermethylation detection in MGMT gene promoter. Results Among the 20 samples,MGMT gene hypermethylation was present in 17 cases（85% ）. The level of hypermethylation in promoter MGMT in colorectal carcinomas was higher than in tissues adjacent（ P 〈 0. 05 ）. Furthermore the levels of 13-15 and 20-23 loci CpG island was much higher than the other three. There was no statistically significant difference of promoter hypermethylation among the samples of different histological grades （ P 〉 0.05 ） or samples with different lymph node metastases （ P 〉 0.05 ）. Conclusions Promoter hypermethylation of MGMT gene is common events in colorectal carcinomas. In addition, MGMT gene has multiple hypermethylation patterns. It suggests that epigenetic inactivation of MGMT plays an important role in colorectal tumorigenesis,although hypermethylation of MGMT gene has not been directly related with tumor progression.

关 键 词：MGMT基因 结 直肠癌 甲基化 微阵列技术 

分 类 号：R735.3[医药卫生—肿瘤] Q786[医药卫生—临床医学]