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