19号染色体微卫星杂合性缺失与原发性胃癌的临床关系

Identification of some macrosatillite sites of chromosome 19 in primary gastric carcinoma with loss of heterozygosity

目的:研究19号染色体短臂微卫星不稳定性(microsatellite instability,MSI)及杂合性缺失(loss of heterozygosity,LOH)与胃癌临床病理特征之间的关系,探讨19号染色体短臂微卫星MSI和LOH的主要临床意义。方法:采用PCR-SSLP-银染方法扩增79例原发性胃癌及正常组织标本中19号染色体短臂不同位置的7个点,PCR产物经聚丙烯酰胺凝胶电泳分离,运用Genescan软件和Genotyper软件分析MSI和LOH,然后进一步分析微卫星LOH与原发性胃癌的临床关系。结果:79例胃癌患者中,至少有1种微卫星发生LOH,其频率为31.18%(27/79),在所有微卫星中,D19S591和D19S565的LOH发生率分别为60.32%(38/63)和48.15%(26/54),高于其他微卫星的LOH。LOH高频率与原发性胃癌的临床分期及远处转移相关,且随着恶性程度增加LOH频率也增加(P<0.05),而MSI与胃癌临床病理之间相关性不大。结论:19p高频率的LOH与原发性胃癌的临床分期和远处转移相关,且LOH高频率提示在该区域可能存在肿瘤抑癌基因,其与胃癌的发生及进展相关。

Objective To investigate the possible correlation between the microsatellite DNA instability （ MSI ） and loss of heterozygosity （ LOH ） on the short ann of chromosome 19 （ 19 p ） and the clinical significance in patients with primary gastric carcinoma, and to explore the importance of MSI and LOH in primary gastric carcinoma. Methods PCR-SSLP -silver stain method was used to detect 7 loci MSI and LOH in 79 primary gastric carcinomas and paired normal control tissues. The PCR products were separated by electrophoresis on polyacrylamide gel. Genescan and genotype soft- wares were used to analyze MSI and LOH. Results LOH with at least one marker on 19p occurred in 31. 18%（27/79）tumors. Among them, LOH at D19S591and D19S565 was 60.32% （38/ 63 ）and 48. 15% （26/54） , respectively. The high incidence of LOH was related to depth of invasion and distant metastases of primary gastric carcinoma （ P 〈 0.05 ） , and there was no significance between MSI and primary gastric carcinoma. Conclusion LOH is related to depth of invasion and distant metastases of primary gastric carcinoma. The high incidence of LOH suggests that there might be putative tumor gene in these LOH sites.