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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星引物 ,扩增相应的微卫星位点 ,平均距离为 10厘摩 (centi morgan ,cM )。用ABIPRISM 3 77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 3 6.78% ,18p中最高为D18S5 3 (3 8.0 9% ) ,18q中最高为D18S474(5 5 .74% )。 4位患者的 18号染色体所有杂合位点都存在缺失 ,3 0位患者的杂合缺失位点不少于 5 0 % (平均 6个 /人 ) ;缺失位点少于 5 0 %的有 5 3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MADH 2、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。
Objective To investigate the suppression of oncogene-associated heterozygosity (LOH) on chromosome 18 in patients with sporadic colorectal cancer and explore new tumor suppressor gene loci. Methods Genomic DNA from 83 cases of patients with sporadic colorectal cancer was amplified with 14 microsatellite primers with highly polymorphic markers. The average microsatellite loci were 10 centiMorgan (cM). The gene was scanned by ABIPRISM 3 77 sequencer, and the rate of loss of heterozygosity at each locus was calculated. Results Among the 12 microsatellite loci with valid data, the average heterozygous deletion rate was 3 6.78%, the highest in 18p was D18S5 3 (3 8.09%), and the highest in 18q was D18S474 (55.74%). All four chromosomes had deletions at all heterozygosities on chromosome 18, with no less than 50% heterozygous deletions (average 6 / person) in 30 patients and less than 50% at 30 5 3 (average 1 / person). Conclusion There is a high frequency of LOH on chromosome 18 in patients with colorectal cancer and is characterized by an overall deletion. In the region of high-frequency LOH, there are TGF-related gene, DCC, RbBP8, especially TGF signaling-related gene MADH2 and 4, transforming growth The loss of factor β1 response element (TGFβ1) and so on may have a significant impact on the occurrence of colorectal cancer. 18p also exists the possibility of unknown tumor suppressor genes.