胃癌和胃癌前病变组织FHIT基因的杂合性丢失

Heterozygosity loss of fragile histidine triad gene in gastric cancer and precancerous lesions

目的:检测脆性组氨酸三联体基因在胃癌和胃癌前病变(肠上皮化生、不典型增生)中的杂合性丢失(LOH), 分析LOH在胃癌发生中的作用. 方法:用PCR的方法检测胃癌42例,不典型增生44 例,肠上皮化生组织5 1例和自身正常对照组织中FHIT基因多态性位点D3S1234,D3S1300的LOH. 结果:胃癌组、不典型增生组、肠上皮化生组在D3S1234 位点的LOH发生率分别为32.4%(11/34),28.6%(10/35), 10%(4/40);在D3S1300位点的LOH发生率分别为33.3% (12/36),32.4%(11/34),7.7%(3/39).胃癌组、不典型增生组在D3S1234和D3S1300位点的LOH发生率显著高于肠上皮化生组.胃癌组和不典型增生组之间在D3S1234, D3S1300位点的LOH发生率均无统计学差异. 结论:FHIT基因的LOH可能是胃癌形成过程中的早期事件,在胃癌发生发展过程可能发挥了一定的作用.

AIM: To detect the loss of heterozygosity (LOH) of fragile histidine triad (FHIT) gene in gastric cancer and precan-cerous lesions (dysplasia and intestinal metaplasia), and to analyze its role in the carcinogenesis of gastric cancer. METHODS: The LOH at microsatellites loci D3S1234 and D3S1300 of FHIT gene were measured in samples of gastric cancer (n = 42), dysplasia (n = 44), intestinal metaplasia (n = 51) and their corresponding normal tissues by (polymerase chain reaction) PCR. RESULTS: The rates of LOH at D3S1234 locus were 32.4% (11/34), 28.6%(10/35) and 10%(4/40) in gastric cancer, dysplasia and intestinal metaplasia respectively, and the ones at D3S1300 locus were 33.3%(12/36), 32.4%(11/34) and 7.7% (3/39) respectively. The LOH rates at D3S1234 and D3S1300 loci in gastric cancer and atypical hyperpla-sia were higher than that of intestinal metaplasia (P<0.05, P<0.01 for D3S1234 and D3S1300 respectively). No significant difference of LOH rate was found between gastric cancer and dysplasia. CONCLUSION: The loss of heterozygosity of FHIT gene may be an early event in the tumorigenesis of gastric cancer.