胃癌家系人群hMLH1基因点突变的分析

Mutation of hMLH1 gene in gastric cancer families

[目的 ]研究我国北方地区胃癌高发人群hMLH1基因突变情况。 [方法 ]取 4个胃癌家系非肿瘤人群 94份和对照人群的 10 0份外周血 ,提取DNA ,聚合酶链反应扩增hMLH1基因的第 8和第 12外显子 ,用毛细管电泳测定外显子的单链构象多态性 ,进而对电泳峰形异常者进行测序。 [结果 ]胃癌家系非肿瘤人群 94例标本中 ,hMLH1基因突变 2 2例 ,突变率 2 3% ,其中第 8外显子突变12例 ,第 12外显子突变 10例 ;10 0例对照标本突变 4例 ,突变率 4 % ,其中第 8外显子突变 2例 ,第12外显子突变 2例。胃癌家系人群hMLH1基因突变率明显高于对照人群 ,且突变的碱基与遗传性非息肉性结肠癌发生突变的碱基位置相同。[结论 ]我国北方地区胃癌高发人群可能有着与HNPCC相似的错配修复基因突变。

[Objective] To study the status of hMLH1 gene point mutations in gastric cancer families from northern China. [Methods] Blood samples from 94 non-cancerous members of four gastric cancer families and control individuals were collected. After DNA abstraction, the mutations of exon8 and exon12 of hMLH1 gene were investigated by PCR-SSCP-CE, followed by DNA sequencing. [Results] The mutant cases were 12 for exon8 and 10 for exon12 of the members in four gastric cancer families, while 2 for exon8 and 2 for exon12 in control individuals. The total mutant rate of the members being 23% in gastric cancer families was significantly higher than that being 4% in control individuals. Moreover, the mutant bases were the same as being found in hereditary nonpolyposis colorectal cancer (HNPCC). [Conclusion] The members of gastric cancer families from northern China may have similar genetic background as those of HNPCC.