中国人遗传性非息肉病性结直肠癌hMLH1与hMSH2基因的种系突变研究  

Study of germline mutation of hMLH1 and hMSH2 in Chinese kindreds of hereditary nonpolyposis colorectal cancer

作　　者：金黑鹰[1] 崔龙[1] 孟荣贵[1] 程慧玉[1] 高军 闫于悌[3] 徐洪莲[1] 喻德洪[1] 

机构地区：[1]第二军医大学附属长海医院肛肠外科,上海200433 [2]解放军海军医学研究所五室 [3]甘肃省人民医院肛肠科

出　　处：《中华胃肠外科杂志》2002年第2期126-129,共4页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金资助项目(39970823)

摘　　要：目的探讨中国人遗传性非息肉病性结直肠癌(HNPCC)患者hMLH1与hMSH2基因的种系突变特点。方法对诊治的6个HNPCC家系的先证者用聚合酶链反应(PCR)的方法扩增其hMLH1及hMSH2的35个外显子,SSCP方法检测其变异,对可疑突变者进行自动测序以确定突变类型。结果6例先证者SSCP检测在3例患者中发现4处异常条带,自动测序证实hMSH211外显子有1处插入突变和1处错义突变、13外显子有1处错义突变,1例在hMLH118外显子及hMSH215外显子均有插入突变。结论中国人HNPCC的错配修复基因突变以hMSH2为主,插入造成的移码突变和错义突变仍为主要病理突变类型。Objective To analysis the features of the germline mutation of hMLH 1 and hMSH 2 in Chinese kindreds of hereditary nonpolyposis colorectal cancer (HNPCC). Method Thirty five exons in hMLH 1 and hMSH 2 of the index cases in 6 chinese HNPCC kindreds were amplified by PCR and their abnormalities were analyzed by SSCP, then the mutation type was determined with automatic sequencer. Results Four abnormal strap were found in 3 of above 6 cases by SSCP. Sequencing showed that exon 11 of hMLH 2 had a insert and a missense mutation and exon 13 had a missense mutation. Another case had insert mutation at exon18 of hMLH 1 and exon 15 of hMSH 2. Conclusions Germline mutation of hMSH 2 dominates in the mutation of the MMR among Chinese HNPCCs. Insertion and missense are main pathogenic mutation.

关 键 词：遗传性非息肉病性结肠直肠肿瘤 基因突变 错配修复 种系突变 分子遗传学 

分 类 号：R735.3[医药卫生—肿瘤]