散发性胆管癌患者染色体3p21.3区段微卫星位点不稳定性分析

目的研究散发性胆管癌患者染色体3p21．3区段的微卫星不稳定性（MSI）及杂合性缺失（LOH），探讨染色体3p21．3区段遗传不稳定性与散发性胆管癌发生发展的关系，定位该区段上散发性胆管癌相关肿瘤基因。方法用聚合酶链反应一单链构象多态性分析（PCR—SSCP）方法检测24例散发性胆管癌患者染色体3p21．3区段上D3S1568、D3S1621、D3S1578和D3S1289四个微卫星位点的MSI和LOH发生率，分析其与临床病理因素之间的关系。结果24例散发性胆管癌组织中，4个微卫星位点的MSI和LOH平均发生率分别为7．23％和15．63％。其中D3S1621位点的LOH最高（45．83％，11／24），并与TNM分期、是否伴有局部／淋巴结转移相关（P〈0．05）。结论染色体3p21．3区段133S1621位点高频率杂合性缺失，提示3p21．3区段定位有散发性胆管癌的候选抑癌基因，并在散发性胆管癌的发生发展过程中发挥重要作用。

Analysis of microsatellite instability at chromosome 3p21.3 in sporadic cholangiocarcinoma patients

Objective To mapping the correlative gene to sporadic cholangiocarcinoma by investigatting microsatellite instability and loss of heterozygosity of chromosome 3p21.3. Methods The MSI and LOH of 4 microsatellite loci D3S1568, D3S1621, D3S1578 and D3S1289 located at chromosome 3p21.3 were detected using PCR-SSCP in 24 sporadic cholangiocarcinoma samples and contral tissues. The relationship between clinical pathology factors and chromosome 3p21.3 instability were analyzed statistically. Results The average ratio of MSI and LOH of 4 microsatellite loci was 7.23% and 15.63% respectively.The highest frequencyof LOH occured at D3S1621 (45.83%, 11/24) and related significently to TNM stages and local or lymphatic metastasis. Conclusion The high frequency LOH of D3S1621 implyed that some candidate gene locate at chromosome 3p21.3 and play an important role in the tumourigenesis of sporadic cholangiocarcinoma.