Telomere erosion is independent of microsatellite instability but related to loss of heterozygosity

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:hngscg
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AIM To correlate the length of the telomere tomicrosatellite instability(MSI)and loss of heterozygosity(LOH)of APC,MCC and DCC genes in gastric carcinomas.METHODS Telomeric restriction fragment(TRF)lengthof gastric cancer was measured with Southern blot.LOHof APC,MCC and DCC genes,microsstellite instability(MSI)and frameshift mutation of hMSH6,TGF-βRⅡ andBAX genes were analyzed by PCR-based methods.RESULTS Sixty-eight cases of sporadic gastriccarcinoma were studied for MSI using five microsatellitemarkers.MSI in at least one locus was detected in 17(25%)of 68 tumors analyzed.Frameshift mutations ofhMSH6,TGF-βRⅡ and BAX were detected in 2,6 and 3 ofgastric carcinomas respectively showing high MSI(≥2loci,n = 8),but none was found in those showing low MSI(only one locus,n = 9)or MSS (tumor lacking MSI orstable,n = 51 ).Thirty-five cases,including all high MSIand low MSI,were studied for TRF.The mean TRF lengthwas not correlated with clinicopathological parameters.No association was observed between TRF length and MSIor frameshift mutation.On the contrary,LOH at the DCClocus was related to telomere shortening (P<0.01).Thistendency was also observed in APC and MCC genes,although there was no statistical significance.CONCLUSION The development of gastric cancer canarise through two different genetic pathways.In high MSIgastric cancers,defective mismatch repair allowsmutations to accumulate and generate the high MSIphenotypa.In gastric cancers showing either low MSI orMSS,multiple deletions may represent the LOH pathway.Telomere erosion is independent of high MSI phenotypabut related to the LOH pathway in gastric cancer. AIM To correlate the length of the telomere tomicrosatellite instability(MSI) and loss of heterozygosity(LOH) of APC,MCC and DCC genes in gastric carcinomas.METHODS Telomeric restriction fragment(TRF)lengthof gastric cancer was measured with Southern blot.LOHof APC, MCC and DCC genes, microsstellite instability (MSI) and frameshift mutation of hMSH6, TGF-βRII and BAX genes were analyzed by PCR-based methods. RESULTS Sixty-eight cases of sporadic gastriccarcinoma were studied for MSI using five microsatellite markers.MSI in at least one Locus was detected in 17(25%) of 68 tumors analyzed.Frameshift mutations ofhMSH6,TGF-βRII and BAX were detected in 2,6 and 3 ofgastric carcinomas showing high MSI(≥2loci,n = 8),but none was found In those showing low MSI (only one locus, n = 9) or MSS (tumor lacking MSI ortable, n = 51 ). Thirty-five cases, including all high MSI and low MSI, were studied for TRF. The mean TRF length was not added With clinicopathological parameters.No association wa s impact between TRF length and MSI frameshift mutation.On the contrary, LOH at the DCClocus was related to telomere shortening (P<0.01).Thistendencywas also observed in APC and MCC genes, therethough there was no statistical significance.CONCLUSION The development of Gastric cancer canarise through two different genetic pathways.In high MSIgastric cancers,defective mismatch repair allows mutations to accumulate and generate the high MSIphenotypa.In gastric cancers showing either low MSI orMSS,multiple deletions may represent the LOH pathway.Telomere erosion is independent of high MSI Phenotypabut related to the LOH pathway in gastric cancer.
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