hMLH1甲基化在散发性大肠癌中的临床意义  

Hypermethylation of hMLH1 promoter in sporadic colorectal cancer

作　　者：宋永茂[1] 袁瑛[1] 郑树[1] 

机构地区：[1]浙江大学医学院附属第二医院,浙江杭州310009

出　　处：《浙江大学学报（医学版）》2004年第5期395-398,共4页Journal of Zhejiang University(Medical Sciences)

摘　　要：目的 :了解散发性大肠癌中 h MLH1基因启动子区域 5 '端 Cp G岛的过度甲基化现象 ,探讨其与微卫星不稳定性 (MSI)在散发性大肠癌发生中的相关性。方法 :取散发性大肠癌患者肿瘤组织及其正常对照组织 (阴性切缘组织 ,距肿瘤 10 cm以上 )标本 4 1对 ,提取 DNA后 ,以甲基化特异性 PCR方法检测标本中 h ML H1启动子的甲基化情况 ,并与相应的临床病理学资料进行统计学分析 ;将 BAT2 5、BAT2 6作为检测位点 ,以自动荧光 DNA序列分析法检测 MSI,并与甲基化情况进行相关分析。结果 :4 1例散发性大肠癌标本中 ,75 .6 % (31/4 1)存在 h ML H1启动子过度甲基化 ,非甲基化患者年龄 (4 9.2岁 )与甲基化患者年龄 (6 3.6岁 )相比差异有显著性 (P<0 .0 5 ) ;4 3.9% (18/4 1)的标本表现为 MSI阳性 ;在 MSI阳性标本中 ,94 .4 % (17/18)有甲基化现象存在 ,明显高于 MSI阴性标本 (6 0 .9% ,14 /2 3) ,两者相比差异有显著性 (P<0 .0 5 )。结论 :散发性大肠癌中普遍存在年龄相关的 h MLH1基因启动子过度甲基化现象 ,由此引起的 MSI可能是老年人大肠癌发病的相关因素之一。Objective: To identify CpG island hypermethylation of 5' region of hMLH1 promotor and to explore its relationship to microsatellite instability(MSI) in sporadic colorectal carcinoma. Methods: Forty one pairs of tissue specimens (normal and cancer) were collected from 41 patients with colorectal cancer. Hypermethylation of hMLH1 promoter was detected by methylation specific PCR; the relationship between methylation and clinicopathological features was analyzed. Combined with BAT25 and BAT26, the MSI status was detected using an automated fluorescent DNA sequencer. Results: Hypermethylation of hMLH1 promoter was detected in 75 6%(31/41) of samples. Mean age of unmethylation cases (49 2 y) was significantly younger than that of methylation cases (63 6 y) ( P <0 05), but there were no differences between two groups in other clinicopathological features. MSI was detected in 43 9% samples (18/41); hypermethylation of hMLH1 promoter was detected in 94 4%(17/18)of MSI(+) samples, which was higher than that in MSI(-) samples (60 9%, 14/23, P <0 05). Conclusion : Age related hypermethylation is generally found in patients with sporadic colorectal cancers, which may cause MSI and might be the mechanism in the development of colorectal cancer of

关 键 词：结直肠肿瘤 病理学 基因 HMLH1 甲基化 微卫星不稳定性 BAT25 BAT26 

分 类 号：R735.3[医药卫生—肿瘤]