胃癌中脆性组氨酸三联体基因异常的检测分析

Detection and analysis of abnormalities of FHIT gene in gastric cancer

目的:检测脆性组氨酸三联体基因在胃癌组织中等位基因缺失和突变情况,分析该异常在胃癌发生中的作用。方法:用PCR鄄SSCP的方法检测36例胃癌和自身正常组织中FHIT基因外显子5、8及多态性位点D3S1300、D3S1234、D3S1312、D3S1313的缺失和突变。结果:肿瘤组织中外显子5有2例(2/36,5.6%)发生缺失,外显子8没有发现缺失;D3S1300的LOH发生率为25%(7/28),MSI为22.2%(8/36);D3S1234的LOH发生率为31%(9/29),MSI为13.9%(5/36);外显子5、8及多态性位点D3S1300、D3S1234、D3S1312、D3S1313的SSCP分析未发现突变。结论:胃癌患者FHIT基因外显子5、8的缺失和突变频率并不高,这种缺失和突变对胃癌的发生到底起多大作用需要进一步探讨;胃癌患者D3S1300、D3S1234位点的LOH、MSI等遗传不稳定现象发生频率较高,能否用于胃癌高危人群筛查和早期诊断值得进一步研究。

Objective:To detect allelic deletion and mutation of FHIT gene in gastric cancer, and to analyze the role of the abnormalities in the carcinogenesis of gastric cancer. Methods:The allelic deletions and mutations of exon 5,8 of FHIT gene and microsatellites D3S1300, D3S1234, D3S1312, D3S1313 were detected in 36 gastric cancer samples and their corresponding normal tissues by PCR-SSCP. Results:Deletion of exon 5 was observed in 2 out of 36 tumor samples, and no deletion of exon 8 was found in tumor samples; The LOH(Loss of heterozygosity) rate at D3S1300 locus was 25%(7/28), and the rate of MSI(microsatellite instability) at D3S1300 was 22.2%(8/36); The LOH rate at D3S1234 was 31%(9/29), and the rate of MSI at D3S1234 was 13.9%(5/36);No mutation was found at exon 5,8 of FHIT gene and microsatellites D3S1300,D3S1234,D3S1312,D3S1313 by SSCP analysis. Conclusion:The rate of deletion and mutation of exon 5,8 of FHIT gene:low in gastric cancer,the exact role of the deletion and mutation of exon 5,8 of FHIT gene in the tumorigenesis of gastric cancer need more research;The rate of LOH and MSI at D3S1300 and D3S1234 loci is relatively high in gastric cancer,which deserve further research on the role of screening and early diagnosis of gastric cancer.