散发性结直肠癌4号染色体等位基因杂合缺失的研究  

Loss of heterzygosity on choromsome 4 in sporadic colorectal carcinoma

作　　者：郑海涛[1] 唐华美[2] 彭志海[1] 李大鹏[1] 周崇治[1] 裘国强[1] 贺林[3] 

机构地区：[1]上海交通大学附属上海第一人民医院普外科,200080 [2]上海交通大学附属上海第一人民医院病理科,200080 [3]上海交通大学BioX生命科学研究中心

出　　处：《中华实验外科杂志》2005年第10期1173-1174,共2页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目(30080016;30470977)

摘　　要：目的通过在4号染色体寻找杂合缺失区域,为定位、筛选高频杂合缺失区存在的散发性结直肠癌相关肿瘤抑制基因提供依据。方法20个荧光标记的微卫星引物与83例结、直肠癌的肿瘤和正常组织进行聚合酶链反应。微卫星的平均遗传距离是10.4里摩(cmol)。产物进行电泳、扫描及杂合缺失分析,并与临床、病理因素进行相关性检验。结果短臂(4p)、长臂(4q)的平均杂合缺失率为24.25%、28.56%,可见3个最小的高频缺失区域(Region):R1:在D4S405和D4S3013(4p1415.2)之间;R2:在D4S3000和D4S2915位点之间(4q1221.1);R3:在D4S407和D4S2939位点之间(4q2531.1)。D4S1534位点与肝脏转移有关(P<0.05),其余位点与临床病理因素均无显著相关(P>0.05)。结论4号染色体的3个高频杂合缺失区域4p1415.2、4q1221.1、4q2531.1存在散发性结直肠癌发生、发展相关的肿瘤抑制基因。Objective To search candidate tumor suppressor genes （TSG） on choromsome 4 via detecting high loss of heterozygosity （LOH） regions in sporadic colorectal carcinoma, Methods Twenty fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and normal tissue DNA by PCR, The average hereditary distance of microsatellite markers was 10.4 cm （centi-Morgan）. PCR products were eletrophoresed and LOH analysis was conducted by Genescan 3.7 and Genotype 3,7 software, Comparison between LOH frequency and clinicopathological factors was per- formed By X2 test. Results The average LOH frequency on 4p and 4q was 24.25% and 28.56% respectively. Three obvious high frequency LOH regions were detected： RI： flanked by D4S405 and D4S3013 locus （4p14-15.2） ; R2： between D4S3000 and D4S2915 locus （4q12-21.1） ; R3： flanked by D4S407 and D4S2939 locus （4q25-31.1 ）. Furthermore, significant difference was observed between LOH frequency and liver metastasis on D4S1534 locus （P 〈 0.05）. No relationship was founded on other loci compared with clinicopathologial features. Conclusion By deletion mapping, we detected three obvious high frequency LOH regions （4p14-15.2, 4q12-21.1,4q25-31.1 ）, which may contribute to locate tumor suppressor genes on chromosome 4 involved in carcinogenesis and progression of sporadic colorectal carcinoma.

关 键 词：结直肠癌 肿瘤抑制基因 染色体 等位基因杂合缺失 4号染色体 临床病理因素 高频杂合缺失 D4S1534 聚合酶链反应 

分 类 号：R735.3[医药卫生—肿瘤]