胃癌错配修复基因hMLH1突变与微卫星DNA不稳的关系

Relationship between mismatching repair gene hMLH1 mutation and microsatellite instability

目的 探讨胃癌错配修复基因hMLH1突变与微卫星不稳 (MSI)的关系。方法 采用PCR为基础的方法检测MSI ;采用二维DNA电泳和DNA测序技术检测hMLH1突变。结果 6 8例胃癌中检出hMLH1基因突变 3例 ,突变率为 4.4%。hMLH1突变与肿瘤大小、分化程度、组织学类型、浸润深度和临床病理分期无显著相关。至少有 1个位点发现MSI者 17例 ( 2 5 .0 % )。将MSI分为高频率MSI(MSI H ,≥ 2个位点 ) 8例、低频率MSI(MSI L ,仅为 1个位点 ) 9例和MSI阴性 (MSS) 5 1例 3组 ,4例hMLH1基因突变均发生于MSI H组 ,而MSI L和MSS组未见有突变者。结论 hMLH1基因突变仅是部分MSI发生的原因 ,MSI的发生可能还涉及到hMLH1以外错配修复基因改变。

Objective To evaluate the role of hMLH1 mutation in gastric carcinogenesis and to correlate hMLH1 mutation with microsatellite instability in gastric carcinomas. Methods hMLH1 mutation was measured by two dimentional DNA electrophoresis and DNA sequencing;MSI was analyzed by PCR based methods. Results Sixty eight cases of sporadic gastric carcinoma were studied for hMLH1 mutation and MSI. hMLH1 mutaions were detected in 3(4.4%)gastric cancer. No association was observed between hMLH1 mutation and tumor size, differentiation, histological type, depth of invasion, metastasis or stages. By using five microsatellite markers, MSI in at least one locus was detected in 17 of 68 (25%) of the tumors analyzed. hMLH1 mutations were all detected in MSI H (≥2 loci, n =8), but no mutation was found in MSI Low (only one locus, n =9) or MSS(tumor lacking MSI or stable, n =51). Conclusion hMLH1 mutation is involved in carcinogenesis of some gastric cancer with MSI H in the majority MSI cases in gastric tumors may be due to defects in other genes responsible for DNA replication fidelity than the hMLH1.