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

查看全文 作　　者：Dian-Chun Fang Shi-Ming Yang Xiao-Dong Zhou Dong-Xu Wang Yuan-Hui Luo Department of Gastroenterology,Southwest Hospital,Third Military Medical University,Chongqing 400038,China 高影响力作者 出　　处：《World Journal of Gastroenterology》索引2001年第7卷第4期,共5页高影响力期刊 基　　金：National Natural Science Foundation of China,No.30070043;'10.5'Scientific Research Foundation of PLA,No.01Z075 摘　　要：AIM To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas.METHODS Telomeric restriction fragment (TRF) length of gastric cancer was measured with Southern blot. LOH of APC, MCC and DCC genes, microsatellite instability (MSI) and frameshift mutation of hMSH6, TGF-βR Ⅱ and BAX genes were analyzed by PCR-based methods.RESULTS Sixty-eight cases of sporadic gastric carcinoma 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 of hMSH6, TGF-βR Ⅱ and BAX were detected in 2,6 and 3 of gastric carcinomas respectively showing high MSI (≥ 2 loci, n = 8), but none was found in those showing Iow MSI (only one locus, n = 9) or MSS (tumor lacking MSI or stable, n = 51). Thirty-five cases, including all high MSI and Iow MSl, were studied for TRF. The mean TRF length was not correlated with clinicopathological parameters.No association was observed between TRF length and MSI or frameshift mutation. On the contrary, LOH at the DCC locus was related to telomere shortening (P< 0.01). This tendency was also observed in APC and MCC genes,although there was no statistical significance.CONCLUSION The development of gastric cancer can arise through two different genetic pathways. In high MSI gastric cancers, defective mismatch repair allows mutations to accumulate and generate the high MSI phenotype. In gastric cancers showing either Iow MSI or MSS, multiple deletions may represent the LOH pathway.Telomere erosion is independent of high MSI phenotype but related to the LOH pathway in gastric cancer. 关 键 词：gastric cancer TELOMERE RESTRICTION FRAGMENT MICROSATELLITE instability loss, HETEROZYGOSITY
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