散发性结直肠癌1p36．33-36．31区域等位基因杂合缺失精细定位  

Refined mapping of loss of heterozygosity of 1p36.33-36.31 in sporadic colorectal carcinoma

作　　者：周崇治[1] 郑海涛[2] 裘国强[1] 张放[1] 贺林[3] 彭志海[1] 

机构地区：[1]上海交通大学附属第一人民医院普通外科,200080 [2]山东大学山东省立医院普通外科 [3]上海交通大学Bio-X生命研究中心

出　　处：《中华医学杂志》2006年第26期1804-1807,共4页National Medical Journal of China

基　　金：国家自然科学基金资助项目(30080016;30470977);上海市卫生局青年科研基金资助项目(局034Y03)

摘　　要：目的抑癌基因的杂合缺失(LOH)被认为是结直肠癌形成的通路之一,本实验通过对染色体1p36．33-36．31区域的杂合缺失精细定位分析,发现高频杂合缺失区域并探讨其意义。方法7个荧光标记的微卫星引物(1p36．33-36．31)与83例结直肠癌的肿瘤和正常组织进行聚合酶链反应(PCR)。产物在ABI Prism 377自动荧光测序仪进行电泳,以GeneSean3．1和Genotyper 2．1软件进行扫描以及杂合缺失分析。杂合缺失结果与临床病理参数之间的关系比较采用X2检验。结果1p36．33-36．31区域平均杂合缺失率是31．5％,以D1S243位点最高,47．2％,最低是D1S1347,7．4％。存在两个高频杂合缺失区域:D1S243位点(1p36．33)以及D1S468和D1S2660位点之间约3 cM的区域(1p36．32-36．31)。1p36．33-36．31区域各位点的杂合缺失率与性别、年龄、肿瘤大小生长方式以及分级无显著相关。结论1p36．33．36．31区域发现了两个高频LOH区域:1p36．33和1p36．32-36．31,可能存在与结直肠癌发生相关的抑癌基因。Objective To screen the candidate tumor suppressor gene （TSG） related to colorectal cancer （CRC）. Methods Seven fluorescent labeled polymorphic markers （ 1p36.33 - 36. 31 ） were analyzed in the samples of tissues of CRC and adjacent normal tissues obtained during operation performed on 83 CRC patients, 40 males and 43 females, aged 31-84. The PCR products were electrophresed. The softwares Genesean 3. 1 and Genotype 2. 1 were used for loss of heterozygosity （LOH） scanning and analysis. Comparison between the LOll frequency and the elinieopathologieal factors was performed by Chisquare test. Results The average LOH frequency in the 1p36.33-36.31 was 31.47%, with the highest LOH frequency of 47.22% at the D1S243 locus and the lowest LOH frequency of 7.35% at the locus D1S1347. Two obvious high LOH regions were detected： D1S1347 locus （1p36.33, about 1 cM） and a region between D1S468 and D1S2660 （1p36.32-36.31about 3 cM）. The LOH rats of the loci in 1p36.33- 36.31 region were not correlated with the age and sex of the patient, and the size, growth pattern, and Dukes stage of the tumor. Conclusion Two obvious high frequency LOH regions, 1p36.32-36.31 and 1 p36.33 have been detected in sporadic CRC where tumor - suppressor - gene（s） may exist.

关 键 词：结肠直肠肿瘤 杂合子丢失 染色体 人 1对 

分 类 号：R735.3[医药卫生—肿瘤]