散发性结直肠癌患者5号染色体杂合缺失分析

目的：探讨散发性结直肠癌患者5号染色体上与抑癌基因相关的杂合缺失（LOH）情况,并探讨新的抑癌基因位点,方法：对83例散发性结直肠癌患者基因组DNA,以15个不同荧光标记的高度多态性微卫星引物（平均遗传距离12．67cm)扩增相应的微卫星位点,用ABI PRISM 377测序仪进行基因扫描,统计各位点杂合缺失率。结果：在15个微卫星位点中,平均杂合缺失率为25．80％,5p中最高为D5S416,占48．15％,5q中最高为D5S471,占38．71％,D5S471周围的3个位点（D5S428,D5S2027 和 D5S2115）也存在高频的杂合缺失（＞30．00％）,结论：5号染色体上存在着高频的杂合缺失,其中5q13.3-31.1区域中,有与结直肠癌发生密切相关的APC,MCC,CTNNA1及IL家族等基因,而在5p15.1上的D5S416的杂合缺失率高达48．15％,此区域至今尚未发现与结直肠癌相关的基因位点,估计可能有未知的抑癌基因存在。

Allelic analysis on chromosome 5 in sporadic colorectal cancer patients

Objective To evaluate and map the putative tumor suppressor loci on chromosome 5 involved in tumor progress or metastasis. Methods Chromosome 5 of 83 patients with sporadic colorectal cancer was systemically screened. Fifteen microsatellite marker primers labeled with 3 different fluorescents were used to amplify the corresponding loci of the genome DNA. The PCR products were electrophoresed on a 377 PRISM sequencer and the fluorescent signals were analyzed with Genotyper and Genescan software. Results The highest loss of heterozygosity (LOH) ratio was found at D5S416(48.15%) on 5p and at D5S471(38.71%) on 5q. The region (5q13.3 31), where D5S471 and 3 neighboring loci (D5S428, D5S2027 and D5S2115) reside, presented high frequent LOH. Conclusion The deletion of APC, MCC, CTNNA1 and IL cluster in the 5q 13.3 31.1 area play important role in the tumorgenesis of colorectal cancer, and the expected existence of another novel tumor suppressor gene on 5p is possible.