袁瑛 黄建 郑树 310009 杭州，浙江医科大学肿瘤研究所 中华肿瘤杂志 1999 0 0 2


    关键词：遗传性非息肉病性结直肠癌；hMLH1；hMSH2；种系突变；家系 期刊 zhzlzz 0 临床研究 fur -->


    

【摘要】 目的 了解29个遗传性非息肉病性结直肠癌(HNPCC)家系中hMLH1和hMSH2基因的种系突变状况。方法 应用PCR-SSCP和DNA测序的方法进行突变筛选。结果 (1)在29个家系中，hMLH1和hMSH2两个基因的总突变率为31.0%，与对照组(2%)相比，差异有极显著性(P<0.01)，其中hMLH1基因是主要的相关基因。(2)10名患大肠癌的家系成员均含有与先证者相同的突变，反映了突变与大肠癌的发生之间有很强的相关性。在29名健康的家系成员中发现了5名突变携带者，为大肠癌的一组高危易感人群。结论 错配修复基因的突变筛选可帮助、指导临床对HNPCC家系进行严密监控。

Mutation of human mismatch repair genes in hereditary nonpolyposiscolorectal cancer (HNPCC) families YUAN Ying, HUANG Jian, ZHENG Shu. CancerInstitute, Zhejiang Medical University, Hangzhou 310009

    【Abstract】 Objective To investigate germline mutations ofmismatch repair genes hMLH1 and hMSH2 in 29 HNPCC families. Methods Mutationswere detected by PCR-SSCP analysis, and confirmed by DNA sequencing. Results (1)In 29 families, the overall mutation rate of these two genes was 31.0% (9/29). Mutationdetected in all of the 9 families was located in the hMLH1 gene, indicating that the hMLH1gene was the main responsible gene in these families. An obvious difference was observedwhen compared to the mutation rate in the control group (P<0.01); (2) All of the 10family members who developed colorectal cancer (CRC) harbored the same mutation asdetected in their proband, indicating a strong association between gene mutation anddevelopment of CRC. In 29 healthy family members, 5 asymptomatic carriers of mutation werefound who were considered as the high-risk populations of CRC. Conclusion Acertain number of HNPCC families can be benefited from the genetic screening for mutationof the mismatch repair genes.

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