16号染色体短臂散发性结直肠癌相关基因的精细定位  

Fine mapping of sporadic colorectal cancer associated gene on chromosome 16p

作　　者：黄力[1] 张放[1] 郑海涛[1] 裘国强[1] 贺林[2] 彭志海[1] 

机构地区：[1]上海市第一人民医院普外科,上海200080 [2]上海交通大学Bio-X生命科学研究中心,上海200032

出　　处：《肿瘤》2005年第6期573-576,共4页Tumor

基　　金：国家自然科学基金(编号:30470977)

摘　　要：目的对散发性结直肠癌16号染色体短臂杂合缺失区间(LOH)进行精细定位,以期发现新的肿瘤相关基因.方法用覆盖16号染色体短臂的5个微卫星标记对83例散发性结直肠癌进行杂合缺失分析,初步定位候选区域后再用另5个微卫星标记对这一区域进行精细定位.PCR扩增相应位点的基因组DNA,并用ABI 377自动测序仪进行电泳.用Genescan 3.7 和Genotype 3.7软件进行遗传位点扫描及杂合缺失分析.杂合缺失与临床病理参数的关系比较采用χ2检验.结果 16号染色体短臂的平均杂合缺失率为24.58%,仅有一高频缺失位点D16S404,杂合缺失率达52.73%.对其精细定位后发现,最小杂合缺失区间应位于D16S406和D16S3126之间,约1.1 cM.而这一区间的杂合缺失与Dukes分期、肿瘤分化及淋巴结转移等无关.结论通过散发性结直肠癌16号染色体短臂杂合缺失的精细定位研究,发现了D16S406～D16S3126之间精度达1.1 cM的肿瘤相关基因候选区域.在这一区间内可能的肿瘤抑制基因为USP7基因,相邻的候选肿瘤抑制基因有EMP2.对这2个基因的深入研究可能明确新的散发性结直肠癌相关基因.Objective To refine the loss of heterozygosity （LOH）on chromosome 16p to identify the new tumor suppressor gene （s）（TSGs） in colorectal tumorigenesis. Methods LOH at 5 microsatellite loci spanning chromosome 16p was detected in 83 cases of sporadic colorectal carcinoma（ SCRC） to define a primary candidate region. And other 5 polymorphic microsatellite markers were employed to refine this region. PCR was employed to amplify the corresponding loci of the genome DNA. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan3.7 and Genotype 3.7 software were used for LOH scanning and analysis. Comparison between LOH and clinlcopathological data was performed by X^2 test. Results The average LOH frequency of chromosome 16p was 24. 58 %, the highest LOH ratio was found at D16S404（52.73 % ）. Fine mapping of this locus identified the minimal region of allelic deletion between D16S406 and D16S3126, the interval was only 1.1 cM. And no relationship was found between LOH in this region and the stage,differentiation or lymph node metastasis of SCRC. Conclusion Through the fine mapping of chromosome 16p, one 1. 1 cM candidate region of tumor related genes was identified. And one putative tumor suppressor gene, USP7,may be in this region, and another potential tumor suppressor gene EMP2 may be very close to this target region. These two genes may play an important role in tumorigenesis of SCRC. The further study about these genes may be helpful to discover novel tumor suppressor gene（s） in SCRC.

关 键 词：结肠直肠肿瘤 基因 肿瘤抑制 染色体 人 16对 杂合子丢失 

分 类 号：R735.3[医药卫生—肿瘤]