遗传性非息肉病性结直肠癌患者hMLH1和hMSH2基因的突变规律

Mutation of hMLH1 and hMSH2 genes in hereditary nonpolyposis colorectal cancer： analysis of 76 probands

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基因的突变特点。方法对76个HNPCC家系先证者的DNA样本用PCR法扩增其hMLH1与hMSH2基因的35个外显子，再进行测序以确定突变类型。结果（1）25个样本发现hMLH1或hMSH2基因突变，总突变率为33％（25／76）；（2）检测到的22种突变中：hMLH1基因突变16个，hMSH2基因突变6个；（3）突变类型包括移码突变、无义突变、剪接区突变、错义突变，其中错义突变较多见（hMLH1基因错义突变11个、hMSH2基因5个）。结论中国人HNPCC家系hMLH1和hMSH2突变谱广泛，突变类型多样，hMLH1突变较hMSH2突变多见。

Objective To investigate the mutations of the mismatch repair genes hMLH1 and hMSH2 in hereditary nonpolyposis colorectal cancer （HNPCC）. Methods The DNA samples of 76 probands of HNPCC families underwent PCR amplification and sequencing on 35 exons in hMLH1 and hMSH2 genes. Results （ 1 ） The overall mutation rate of the hMLH1 and hMSH2 genes was 33% （ 25/ 76）. （2）22 mutations were found, 16 in the hMLH1 gene and 6 in the hMSH2 gene. （3）The spectrum of mutation type included frame shift,nonsense,splice site,and missense mutations. Missense mutation was the most common mutation type. Conclusion The hMLH1 and hMSH2 mutations in Chinese HNPCC families show a wide spectrum. It seems that hMLH1 gene is involved more frequently than hMSH2 gene. A certain number of HNPCC families can be benefited from the genetic screening for mutation of the mismatch repair genes.