散发性结直肠癌患者18号染色体高频杂合缺失的研究

目的：探讨散发性结直肠癌患者18号染色体上抑癌基因相关的杂合缺失（LOH）情况，并探索新的抑癌基因位点。方法：对83例散发性结直肠癌患者基因组DNA用14个不同荧光标记的高度多态性微卫生引物，扩增相应的微卫星位点，平均距离为10厘摩（centi-morgan,cM）。用ABI PRISM377测序仪进行基因扫描，统计各位点杂合缺失率。结果：在12个获得有效数据的微卫星位点中，平均杂合缺失率为36．78％,18p中最高为D18S53（38．09％），18q中最高为D18S474（55．74％）。4位患者的18号染色体所有杂合位点都存在缺失，30位患者的杂合缺失位点不少于50％（平均6个／人）；缺失位点少于50％的有53人（平均1个／人）。结论：结直肠癌患者18号染色体存在高频的LOH，并以整体缺失为特点。存在高频LOH的区域定位有转化生长因子（TGF）信号传导相关基因、结直肠癌缺失基因（DCC）、Rb结合蛋白8(RbBP8），特别是TGF信号传导相关基因MADH2、4、转化生长因子－β1反应元件（TGF－β1）等的缺失可能对结直肠癌的发生有重要影响。18p也有存在未知抑癌基因的可能。

High frequency of LOH on chromosome 18 in Chinese sporadic colorectal cancer patients

Objective To study the tumor suppressor gene (TSG) related loss of heterozygosity (LOH) on chromosome 18 in sporadic colorectal cancer.Methods Forteen microsatellite marker primers labeled with 3 different fluorescents were applied to amply the corresponding loci of the genome DNA.The PCR products were electrophoresed on a 377 PRISM sequencer and the fluorescent signals were analyzed by Genotyper and Genescan software.Results The highest LOH ratio was seen at D18S53 (36.67 %) on 18p and at D18S474 (56.14 %) on 18q.There were 4 patients whose markers of chromosome 18 deleted entirely.The percentages of LOH in 30 patients were no less than 50 %,and that of other 53 patients was less than 50 %.Conclusion A highly frequent LOH was found on chromosome 18 in sporadic colorectal cancer patients,which implicated that the deletion of DCC,RBBP8 and TGF signal related genes (MADH2,MADH4 and TGFBRE) might play important roles in the tumorigenesis of colorectal cancer,and that the existence of another unknown TSG on 18p is possible.