中国人胃癌组织微卫星DNA的杂合性缺失研究

Studies of loss of heterozygosity(LOH) in Chinese human gastric cancer tissues

目的从多位点筛选中国人胃癌的杂合性缺失（ＬＯＨ）频率，以初步确定与胃癌的致病基因连锁最密切的ＭＳｍａｒｋｅｒ。方法选择了３０个多态微卫星标记，采用ＰＣＲ、聚丙烯酰胺凝胶电泳及银染技术，对４２例胃癌组织进行了ＬＯＨ分析。结果在２９个位点上检测到总的ＬＯＨ频率为２７．７％。高频率的ＬＯＨ主要集中在Ｄ３Ｓ１５７７、Ｄ３Ｓ１０６７、Ｄ６Ｓ４３０、Ｄ１５Ｓ２０５、Ｄ１７Ｓ９４５等位点。ＬＯＨ频率均在４０％以上。其次是Ｄ５Ｓ４０７、Ｄ２Ｓ１３６、Ｄ２Ｓ１４７、Ｄ１３Ｓ１７５、Ｄ１４Ｓ６８、Ｄ８Ｓ２７９，其ＬＯＨ频率均在３０％以上。不同病理分型的胃癌，ＬＯＨ频率存在明显差异。印戒细胞癌的ＬＯＨ明显高于低分化胃癌（Ｐ＜０．０１）；低分化胃癌的ＬＯＨ频率亦明显高于高分化胃癌（Ｐ＜０．０１）。４例高分化胃癌均未发现ＬＯＨ。结论高频率的ＬＯＨ位点附近，除了已克隆的癌基因、抑癌基因外，可能还含有未知的胃癌易感基因。这一结果表明。

Objective To identify the LOH frequency in Chinese gastric cancer samples and locate lost region of gastric cancer related tumor suppressor gene. Methods Thirty microsatellite markers were used to examine 42 cases of tumor normal paired gastric cancer tissues for LOH on all chromosomes (except Y) using polymerase chain reaction(PCR). Results The total frequency of LOH in 42 gastric cancer was 27.7%. High frequencies of LOH(≥40%) were observed at loci D3S1067,D3S1577, D6S430, D15S205, D17S945, and D5S407,D2S136,D2S147,D13S175,D14S68,D8S279 loci had LOH frequency≥30%. Significantly more LOH cases were observed in the poorly differentiated type and the signet cell type than in well differentiated type of gastric cancers ( P =0.00699 and 0.0001). The incidence of LOH in signet cell cancer was even significantly higher than that in poorly differentiated gastric carcinomas( P =0.0019). LOH was not found in 4 cases with well differentiated gastric cancer. Conclusion The most common LOH occurred at D3S1577,D3S1067,D5S407,D6S430,D8S279,D15S205 and D17S945 might imply the existence of potential tumor suppressor genes of gastric cancer.