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目的 :针对胃癌发生、发展过程中多基因变异的特性 ,鉴定几类与肿瘤相关的基因在胃癌中的改变 ,进一步探讨其与肿瘤易感性的关系。方法 :选择c met原癌基因、错配修复基因hMLH1、E cadherin基因以及HLA Ⅱ类区的 (DQA1、DR2、DR3、DR4、DR7、DR9) 6个基因位点 ,采用PCR系列技术对 32例肠型胃癌标本和 4个胃癌细胞系进行检测以确定上述基因在肠型胃癌中的变异情况。结果 :在c met基因第 17、18和 19外显子未检测到点突变。对错配修复基因hMLH1的D3S12 98和D3S15 6 1两个位点进行微卫星不稳定性 (microsatelliteinstability ,MSI)和杂和性缺失 (lossofheterozygosity ,LOH)检测 ,其中在D3S12 98位点检测到 6例MSI,2例LOH ,D3S15 6 1位点有2例检测到MSI。在E cadherin基因附近选择两个微卫星位点D16S30 83和D16S30 95进行MSI和LDH检测 ,D16S30 83位点有 4例检测到MSI ,2例有LOH ,D16S30 95位点未检测到MSI和LOH。HLA Ⅱ类基因区 6个基因位点基因型在个体中存在着明显多态性 ,PCR SSCP结果显示DR4基因位点有较高频率的变异 (9/ 2 0 ) ,明显高于其它几个基因位点。结论 :c met原癌基因在胃癌中的变化方式不是以点突变为主 ,hMLH1、E cadherin基因在肠型胃癌中有明显改变 ,HLA Ⅱ类基因区DR4基因的变异可能与?
Objective: To identify the characteristics of multiple gene mutations during the development and progression of gastric cancer, identify the changes of several tumor-related genes in gastric cancer, and further explore their relationship with tumor susceptibility. METHODS: Six gene loci of c-metagene, mismatch repair genes hMLH1, E cadherin and HLA class II (DQA1, DR2, DR3, DR4, DR7, and DR9) were selected. PCR was used for 32 cases. Gastrointestinal gastric cancer specimens and four gastric cancer cell lines were tested to determine the variability of these genes in intestinal type gastric cancer. RESULTS: No point mutations were detected in exons 17, 18, and 19 of the c met gene. Microsatellite instability (MSI) and loss of heterozygote loss (LOH) were detected in two sites of mismatch repair gene hMLH1 D3S12 98 and D3S15 61. Among them, 6 cases were detected at D3S12 98 loci. MSI, MSI was detected in 2 patients with LOH and D3S15 61 sites. Two microsatellite loci D16S30 83 and D16S30 95 were selected in the vicinity of the E cadherin gene for MSI and LDH detection. MSI was detected in 4 of the D16S30 83 loci, and LOH was detected in 2 of the 83 loci. No MSI and LOH were detected in the D16S30 95 locus. The genotypes of the six gene loci in the HLA class II gene region are significantly different in individuals. PCR SSCP results show that the DR4 gene locus has higher frequency variation (9/20), which is significantly higher than several other genes. Location. Conclusion : The change of c-metagenes in gastric cancer is not based on point mutations. The hMLH1 and E-cadherin genes are significantly changed in intestinal type gastric cancer. The variation of DR4 gene in HLA class II gene region may be related to?