胃癌FHIT基因杂合性缺失及微卫星不稳定性的研究

Study of loss of heterozygosity and microsatellite instabilities of fragile histidine triad gene in gastric carcinoma

目的:检测胃癌FH IT基因的杂合性缺失(LOH)和微卫星不稳定性(MSI),探讨其与胃癌临床病理特征的关系。方法:从染色体3p14.2选取4个微卫星标记,PCR方法检测50例胃癌和远端正常胃黏膜组织FH IT基因的LOH和MSI。结果:胃癌组织中FH IT基因LOH和MSI发生的平均频率分别为32.4%和26.4%。LOH和MSI与胃癌的Borm ann分型、组织学类型、Lauren分型均无显著相关。LOH阳性率胃癌穿透浆膜组显著高于未穿透浆膜组(P<0.05)。MSI阳性率无淋巴结转移组显著高于有淋巴结转移组(P<0.05)。结论:FH IT基因的MSI参与胃癌发生的早期阶段,LOH对胃癌的发展演变起重要作用。

Objective： To detect the loss of heterozygosity （LOH） and microsatellite instabilities （MSI） of fragile hisfidine triad （FHIT） gene and their association with the clinical pathological characteristic of gastric carcinoma（GC）. Methods： LOH and MSI of FHIT were detected at four microsaterUite loci ：D3S 1300, D3S 4103, D3S 1481 ,and D3S 1234 by using PCR in matched normal and cancer tissues from 50 patients with primary GC. Results：The average frequencies of LOH and MSI of FHIT gene in GC were 32.4% and 26.4% respectively. LOH and MSI of FHIT gene in GC had no association with histological, Borrmann, and Lauren＇s classification. LOH of FHIT gene in GC was related to invasive depth and the frequency of LOH in GC with seroal infiltration was obviously higher than that in GC without serosal infiltration （73.5% wersus 37.5%, P 〈 0.05）. MSI of FHIT gene in GC was associated with the lymph node metastasis,and the frequency of MSI in GC without lymph node metastasis was significantly higher than that in GC with lymph node metastasis （66.7% wersns 34.3%, P 〈 0.05）. Conclusion： LOH of FHIT gone was correlated with invasive depth of GC. MSI of FHIT gene was correlated with lymph node metastasis. LOH and MSI of FHIT genemay play an important role in the carcinogenesis of GC.