散发性结直肠癌1号染色体短臂遗传位点杂合缺失  

Loss of heterozygosity on the genetic loci of the short arm of chromosome 1 in sporadic colorectal carcinoma

作　　者：裘国强[1] 周崇治[1] 张放[1] 贺林[2] 彭志海[1] 

机构地区：[1]上海市交通大学附属第一人民医院普通外科,上海200080 [2]上海交通大学Bio-X生命科学研究中心,上海200030

出　　处：《肿瘤》2007年第1期51-54,共4页Tumor

基　　金：国家自然科学基金资助项目(编号:30080016)

摘　　要：目的:抑癌基因的杂合缺失(loss of heterozygosity,LOH)被认为是结直肠癌形成的关键步骤之一。本实验研究了结直肠癌1号染色体短臂杂合的缺失情况,并探讨其临床意义。方法:选取11个微卫星DNA标记与83例结直肠癌病例的肿瘤和正常组织进行PCR。PCR产物在ABIPrism377自动荧光测序仪上进行电泳,以GeneScan3.1和Genotyper2.1软件进行遗传位点扫描以及杂合缺失分析。结果:1号染色体短臂的平均杂合缺失率为18.00%,D1S468(1p36.33-36.31)位点的杂合缺失率最高,达36.54%。D1S2726位点的杂合缺失现象主要存在于直肠癌,缺失率为28.57%(6/21),而结肠癌的缺失率为0.00%(0/33),二者差异具统计学意义(P=0.002)。结论:在1号染色体短臂上可能存在与结直肠癌发生相关的抑癌基因,位于1p36.33-36.31这个区域。Objective：The loss of heterozygosity （LOH） on tumor suppressor genes is believed to play a key role in carcinogenesis of colorectal cancer. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. In this study, the LOH on the short arm of chromosome 1 in sporadic colorectal cancer was analyzed in colorectal tumorigenesis. Methods：Eleven polymorphic microsatellite markers were analyzed in 83 cases of colorectal and normal DNA by polymerase chain reaction （PCR）. PCR products were eletrophoresed on an ABI 377 DNA sequencer; Genescan 3.1 and Genotype 2.1 software were used for loci scanning and LOH analysis. Comparison between LOH frequency and clinicopathological data were performed by X^2 test. P〈0.05 was considered as statistically significant. Results： The average LOH frequency of the short arm of chromosome 1 was 18.00%. The highest LOH locus with frequencies of 36.54% was identified on D1S468 （lp36.33-p36.31）. On D1S2726 locus, LOH mostly occurred in rectal cancer, with frequency of 28.57% （6/ 21）, which was higher than that of colon cancer （0.00%, 0/33） （P=0. 002）, suggesting the mechanism of carcinogenisis was different in both groups. Conclusion： This study provides the evidence for the involvement of putative tumor suppressor genes related to the sporadic colorectal carcinoma on the short arm of chromosome 1, The tumor suppressor gene（s） might locate on the lp36.33-36.31.

关 键 词：结肠直肠肿瘤 杂合子丢失 染色体 人 1对 

分 类 号：R735.34[医药卫生—肿瘤] R730.23[医药卫生—临床医学]