AIM： To investigate loss of heterozygosity （LOH） and microsatellite instability （MSI） on the chromosomal region 1p36-pter in cholangiocarcinoma （CCA） patients and determine the association between microsatellit...AIM： To investigate loss of heterozygosity （LOH） and microsatellite instability （MSI） on the chromosomal region 1p36-pter in cholangiocarcinoma （CCA） patients and determine the association between microsatellite alterations and clinicopathological parameters. METHODS： Ten polymorphic microsatellite markers were determined for LOH and MSI using GS-3000 gel scan fragment autoanalyzer. RESULTS： Sixty-eight out of 90 cases （75.6%） showed LOH in one or more loci. LOH was found most frequently at DIS199 （40.0%）, DIS507 （34.6%）, DIS2845 （30.5%）, and DIS2734 （30.1%）. MSI was found in 34 of 90 cases （37.8%） at one or more loci. Fine mapping at lp36 showed two distinctive regions of common loss, which were D1S2845 and the 25.5-cM region between D1S507 and D1S2734, indicating the existence of putative tumor suppressor genes that is likely to play important roles in the development of CCA. Patients with LOH at D1S234 showed less lymphatic invasion （P = 0.017）, whereas patients with LOH at D1S2676 exhibited more lymphatic invasion than those without （P = 0.031）. LOH at D1S2845 showed a significant correlation with nerve invasion （P = 0.029）. Moreover, patients who demonstrated MSI at D1S228 showed a poor prognosis （P = 0.0026）. CONCLUSION： Allelic loss plays a major role in microsatellite alterations at chromosome lp36, which may contribute to carcinogenesis and pathogenesis of liver fluke related CCA and these alterations can be used as molecular prognostic indicators for CCA patients.展开更多
基金Supported by the National Center for Genetic Engineering and Biotechnology (BIOTEC)the National Science and Technology Development Agency (NSTDA), Thailand, No. BT-B-06-MG-12-4405
文摘AIM： To investigate loss of heterozygosity （LOH） and microsatellite instability （MSI） on the chromosomal region 1p36-pter in cholangiocarcinoma （CCA） patients and determine the association between microsatellite alterations and clinicopathological parameters. METHODS： Ten polymorphic microsatellite markers were determined for LOH and MSI using GS-3000 gel scan fragment autoanalyzer. RESULTS： Sixty-eight out of 90 cases （75.6%） showed LOH in one or more loci. LOH was found most frequently at DIS199 （40.0%）, DIS507 （34.6%）, DIS2845 （30.5%）, and DIS2734 （30.1%）. MSI was found in 34 of 90 cases （37.8%） at one or more loci. Fine mapping at lp36 showed two distinctive regions of common loss, which were D1S2845 and the 25.5-cM region between D1S507 and D1S2734, indicating the existence of putative tumor suppressor genes that is likely to play important roles in the development of CCA. Patients with LOH at D1S234 showed less lymphatic invasion （P = 0.017）, whereas patients with LOH at D1S2676 exhibited more lymphatic invasion than those without （P = 0.031）. LOH at D1S2845 showed a significant correlation with nerve invasion （P = 0.029）. Moreover, patients who demonstrated MSI at D1S228 showed a poor prognosis （P = 0.0026）. CONCLUSION： Allelic loss plays a major role in microsatellite alterations at chromosome lp36, which may contribute to carcinogenesis and pathogenesis of liver fluke related CCA and these alterations can be used as molecular prognostic indicators for CCA patients.
