摘要
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 。
Objective To explore the relationship of the telomere length to microsatellite instability (MSI) and to loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas. Methods The specimens were collected from 68 cases of gastric cancer. The length of telomeric restriction fragment (TRF) was measured with Southern blot. LOH of APC, MCC and DCC genes, MSI and frameshift mutation of hMSH6, TGF βRⅡ and BAX genes were analyzed with PCR based methods. Results Among all 68 samples, MSI was found in 17 (25%), including 8 of MSI High (≥2 loci) and 9 of MSI Low (only one locus). The left 51 samples were found to be lacking MSI or microsatellite stability (MSS). Out of the 8 cases of MSI High, frameshift mutation of TGF βRⅡ, BAX and hMSH6 genes was showed in 6, 3 and 2 cases respectively, but no mutation of these genes was found in MSI Low and MSS samples. In 35 cases, including all MSI High and MSI Low studied for TRF, TRF length was shown to be shorter in 20 cases (57.1%), similar in 12 (34.3%) and elongated in 3 (8.6%). The mean TRF length had no correlation with clinicopatho logical parameters. No association was observed between TRF length and MSI or frameshift mutation. But LOH at the DCC locus were associated with 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 occur through 2 different genetic pathways. In MSI High gastric cancers, defective mismatch repair leads the accumulation of mononucleotide mutation and the demostration of MSI High phenotype. In gastric cancers showing MSI Low or MSS, multiple deletions may represent the LOH pathway. Telomere erosion might participate in the LOH pathway but be unassociated with MSI High phenotype in gastric cancer.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2001年第1期2-5,共4页
Journal of Third Military Medical University
基金
国家自然科学基金资助项目! ( 396 70 347)
关键词
胃癌
端粒限制性片段长度
染色体不稳
微卫星
DNA
gastric carcinoma
length of telomeric restriction fragment
chromosome instability
microsatellite instability
