HNPCC患者错配修复基因转录调控因子作用分析

In this study,we collected and followed up 50 typical and nontypical HNPCC kindreds.The clinicopthological features of the Chinese HNPCC were study and a new criteria of the nontypical HNPCC was defined and its clinical significence was studies.The germline mutation of hMLH1 and hMSH2 of 12 index cases of 6 nontypical HNPCC and 6 typical HNPCC were study using PCR-SSCP and sequencing. Senven germline mutations in 6 cases were found. Especially,one case had the germline mution of hMLH1 and hMSH2 spontanously.The expression of hMLH1 and hMSH2 were analysed with immunohistochemistry method. We also study the significant of MSI in screening the HNPCC families . The promoter of hMLH1 and hMSH2 were studied in our program.We found a novel germline mutation in one cases. The P53 mutaion was exclusive from the germline mutaion of hMLH1 and hMSH2,which might imply a new path of HNPCC carcinogenesis.

从典型及不典型HNPCC患者肿瘤组织及正常淋巴细胞中提取基因组DNA，PCR-SSCP法检测6种MMR基因突变。选择无MMR编码区变异的患者，PCR法克隆其正常组织及肿瘤组织MMR基因启动有蛄胁⒓右员冉希奔觳庹Ｗ橹爸琢鲎橹疨53基因的变异。构建由该启动子调控报告基因的载体并分别将其转染至P53基因正常及异常的肿瘤细胞系，检测报告基因活性以分析寺⌒蛄蠵53蛋白的结合作用，为进一步阐明HNPCC的发病机理及临床诊断奠定基础。