摘要
目的:检测错配修复基因hMLH3在家族性胃癌中的突变情况,以探讨hMLH3在家族性胃癌中的作用. 方法:采用聚合酶链反应(PCR)、变性高效液相色谱分析(DHPLC)和直接测序法,检查有遗传背景的16个胃癌家系(共84名成员)的错配修复基因hMLH3突变情况.胃癌家系选择参考以下标准:(1)至少连续两代;(2)至少2例胃癌患者;(3)至少有1例患者为其他患者的一级亲属;(4)至少有1 例患者50岁前被诊断出胃癌. 结果:所有样品的外显子均成功进行PCR扩增,DHPLC分析和基因测序.共在5个家系中发现5处错义突变(31.3%, 5/16),4处在外显子1,另外1处在外显子12.家系6中hMLH3的突变与胃癌发生呈现出较强的相关性,而另外几个家系中的突变情况与胃癌没有表现出明显的相关性.在散发性胃癌及正常对照中未发现突变的存在. 结论:hMLH3基因在家族性胃癌发生中可能为一低风险基因,他可能通过与其他基因互相叠加、共同起作用.
AIM: To detect the mutations of mismatch repair gene hMLH3 and to investigate its possible role in familial gastric cancer. METHODS: A total of 84 members from 16 suggestive hereditary gastric cancer families were investigated with PCR, denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. The diagnostic criteria for familial gastric cancer are as follows: (1) at least two successive generations, (2) at least two patients with gastric cancer, (3) one of them should be first-degree relative of the other, and (4) at least one patient was diagnosed before 50 years old. RESULTS: Five missence mutations were identified in five gastric cancer families, four mutations within exon 1 and one mutation within exon 12. Carcinogenesis was obviously associated with hMLH3 mutations in family 6, but not in other families. No mutations were found in sporadic gastric cancer and normal controls. CONCLUSION: hMLH3 probably acts as a low risk gene in familial gastric cancer. The mutations of hMLH3 may work together with other genes and result in an elevated risk of gastric cancer in the family.
出处
《世界华人消化杂志》
CAS
2004年第5期1030-1033,共4页
World Chinese Journal of Digestology
