散发性结直肠癌染色体20q11—13区杂合性缺失精细定位

Fine mapping of heterozygosity loss on chromosome 20q11-13 in sporadic colorectal cancer

目的研究散发性结直肠癌20号染色体杂合性缺失情况，并对20q11-13区进行精细定位。方法收集1998年至1999年上海市第一人民医院83例结直肠癌患者的肿瘤组织和对应的正常黏膜组织，采用10个微卫星标记的引物对20号染色体进行杂合性缺失分析，在20q11-13区域另取10个微卫星标记的引物并对标本进行PCR分析。以Genescan 3．1和Genotyper 2．1软件进行基因分型和精确定位。结果在20号染色体上发现一个高频杂合性缺失区即20q11-13区。进一步的精细定位，界定了两个高频杂合性缺失区：20q11．2、20q12，并在该杂合性缺失区发现了抑癌基因E2F1、PMP24和MAFB。结论20号染色体有两个高频精细杂合性缺失区，该区很可能存在一个或多个与结直肠癌相关的新的抑癌基因。

Objective To refine the loss of heterozygosity（LOH） on chromosome 20q11-13 and identify the new tumor suppressor gene（s） in coloreetal tumorigenesis. Methods From 1998 to 1999, 83 patients with eoloreetal cancer had been admitted to Shanghai First People＇s Hospital. Tumor tissues and adjacent normal mucosal tissues were collected. Ten polymorphic microsatellite markers were analyzed on chromosome 20 and another 10 markers were applied on chromosome 20q11-13 in 83 cases of coloreetal and normal DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genesean 3.1 and Genotyper 2.1 software were used for LOH scanning and analysis. Results We observed a distinct region of frequent allelie deletions on chromosome, another 10 polymorphrie microsatellite markers were applied to 20q11-13 and 2 minimal regions of frequent LOH were established, that is to say 20ql 1.2, 20q12. Tumor suppressor genes E2F1, PMP24 and MAFB were found in the regions of 20qll. 2 and 20q12. Conclusion Through our detailed deletion mapping studies, we have found 2 critical and precise regions, which must contain one or more unknown tumor suppressor gene （s） on colorectal cancer.