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目的 探讨端粒长度与微卫星不稳定 (MSI)和APC MCC及DCC基因杂合丢失 (LOH)的关系。方法 采用Southern杂交检测端粒限制性片段长度 ;采用PCR为基础的方法对MSI、LOH和移码突变进行分析。结果 68例胃癌中 ,至少有 1个位点发现MSI者 17例 (2 5 % )。将MSI分为高频率MSI(≥ 2个位点 ) 8例、低频率MSI(仅为 1个位点 ) 9例和MSI阴性 5 1例 3组 ,结果 8例高频率MSI中检出TGF βRⅡ移码突变 6例 ,BAX移码突变 3例 ,hMSH6移码突变 2例 ,而低频率MSI和MSI阴性组未见有移码突变者。3 5例胃癌行TRF分析 ,其中端粒缩短 2 0例 (5 7.1% ) ,基本不变 12例 (3 4 .3 % ) ,延长 3例 (8.6% )。端粒长度与临床病理参数无关。DCC基因LOH与TRF缩短有关 ,APC和MCC基因亦有随TRF缩短而LOH率增高的倾向。TRF长度与MSI和移码突变无相关性。结论 胃癌发生涉及二条不同的分子途径。高频率MSI胃癌由于错配修复基因缺陷导致单核苷酸水平突变的积聚和高频率MSI表型 ,而低频率MSI和MSI阴性胃癌可能涉及LOH病理途径。端粒丢失可能参与了LOH病理途径 ,而与MSI途径无关
Objective To investigate the relationship between telomere length and microsatellite instability (MSI) and loss of heterozygosity (LOH) in APC MCC and DCC genes. Methods The restriction fragment length of telomere was detected by Southern blotting. The PCR-based MSI, LOH and frameshift mutations were analyzed. Results In 68 cases of gastric cancer, MSI was found in at least 1 locus in 17 cases (25%). The MSI was divided into high frequency MSI (≥ 2 sites) in 8 cases, low frequency MSI (only 1 site) in 9 cases and MSI negative 5 1 cases and 3 groups. Results 8 cases of high frequency MSI detected TGF β R Ⅱ There were 6 cases of frameshift mutation, 3 cases of BAX frame shift mutation and 2 cases of hMSH6 frameshift mutation, while there was no frameshift mutation in low frequency MSI and MSI negative group. In TRF analysis of 35 cases of gastric cancer, telomere shortening was 20 cases (51.14%), unchanged in 12 cases (34.4%) and prolonged in 3 cases (8.6%). Telomere length has no relation with clinicopathological parameters. DCC gene LOH and TRF shortening related, APC and MCC gene also with TRF shortening and LOH rate tends to increase. There was no correlation between TRF length and MSI and frameshift mutations. Conclusions Gastric cancer involves two different molecular pathways. High-frequency MSI gastric cancer results in accumulation of single nucleotide level mutations and high-frequency MSI phenotypes due to mismatch repair gene defects, whereas low-frequency MSI and MSI-negative gastric cancers may be involved in LOH pathology. Telomere loss may be involved in pathological LOH pathways, and has nothing to do with the MSI pathway