散发性结肠直肠癌肿瘤分化及转移相关基因杂合缺失分析  

Loss of heterozygosity analysis to difine putative region involved in tumor differenciation and metastases in sporadic colorectal cancer patients

作　　者：彭志海[1] 张放[1] 周崇治[1] 裘国强[1] 柏邵春[2] 刘万清[2] 贺林[2] 

机构地区：[1]上海第一人民医院普外科,200080 [2]中国科学院上海生理所

出　　处：《中华外科杂志》2002年第10期776-779,共4页Chinese Journal of Surgery

基　　金：国家自然科学基金资助项目 (3 0 0 80 0 16)

摘　　要：目的　探讨散发性结肠直肠癌患者 2号染色体上可能的肿瘤转移相关基因位点。方法　以 2号染色体上 30个不同荧光标记的高度多态性微卫星引物对 83例散发性结肠直肠癌患者基因组DNA扩增相应的微卫星位点 ,用ABIPRISM 377测序仪进行基因扫描 ,检测各位点杂合缺失率 ,比较与肿瘤分期、分化的关系。结果　 2 4个位点获得有效数据 ,平均遗传距离为 11厘摩 (cM) ,杂合缺失率平均为 15 16 % ,较高的有 2个位点 :D2S2 0 6 (2q33 37)的 32 0 8%和D2S36 4 (2q32 1)的31 0 3% ,其余位点的杂合缺失率均小于 2 0 0 0 % ;D2S14 2 (2q2 4 1)、D2S12 6 (2q35 )、D2S2 2 11(2p2 4 2 )、D2S30 5 (2p2 3 3)的杂合缺失率随着肿瘤恶性程度的增加而增高 ,后 2个位点间的缺失有相关性。结论　已知几个错配修复基因位点附近的微卫星位点并无高频杂合缺失发生 ,D2S30 5 (2p2 3 3)到D2S2 2 11(2p2 4 2 )之间区域为整体性缺失 ,此区域和D2S14 2 (2q2 4 1)、D2S12 6 (2q35 ) 2个位点与肿瘤的恶性程度相关 ,提示存在未知的肿瘤分化和转移相关基因的可能。Objective To detect putative suppressor loci involved in tumor progressing or metastases. Methods Thirty microsatellite marker primers were employed to amply the corresponding loci of the genome DNA from 83 patients with sporadic colorectal cancer. The PCR products were electrophoresed on a 377 PRISM sequencer and the fluorescent signals were analyzed by Genotyper and Genescan software. Results The data were obtained from 24 loci,with an average LOH frequency of 15 16%. The LOH at D2S206 and D2S364 was more frequent than 30%, and was less than 20% at the rest loci. Significant difference was observed between the percentage of LOH and tumor staging or differentiation at D2S142(2q24 1), D2S126(2q35), D2S2211(2p24 2), D2S305(2p23 3). Occarrence of deletion at the later two loci was correlative. Conclusions Frequent LOH was not observed at the loci around known mismatch repair genes on chr.2. The region between D2S305(2p23 3) and D2S2211(2p24 2) deleted holistically, and was correlated to the stage and differentiation of tumor attended by D2S142(2q24 1) and D2S126(2q35) on 2q It is suggested that unknown genes associated with tumor progressing or metastases reside in the two loci on 2q or the region on 2p.

关 键 词：散发性 直肠癌 肿瘤分化 杂合子丢失 肿瘤转移 结肠肿瘤 微卫星位点 

分 类 号：R735.3[医药卫生—肿瘤]