膀胱癌等位基因缺失研究  

Allelic Loss in Bladder Cancer

作　　者：李光[1] 张海峰[2] 徐妙生[1] 王全红[3] 

机构地区：[1]首都医科大学附属北京天坛医院病理科 [2]山西省太原市第二人民医院检验科 [3]山西省肿瘤医院病理科

出　　处：《首都医科大学学报》2008年第1期81-84,共4页Journal of Capital Medical University

摘　　要：目的了解膀胱癌克隆演变(clonal evolution)过程中的遗传学机制。方法分别利用4个位于染色体9p21区和17p13区上具有多态性的微卫星标记物,分析了18位膀胱癌病人原发癌及相应转移灶中等位基因的缺失或保留方式。利用显微切割技术在保存的石蜡包埋组织中获取基因组DNA。结果在原发癌和转移灶中总的等位基因缺失频率均为89%(16/18),而在原发癌中D9S161的缺失频率为86%,D9S171为67%,IFNA71%,TP5380%;在转移灶中各位点缺失频率分别为100%(D9S161),67%(D9S171),71%(IFNA),80%(TP53)。18例病例中,16例(89%)在原发癌及相应转移灶中所有位点均表现为相同的等位基因缺失或保留模式,而另外2例(11%)则显示不一致的等位基因缺失。这2例在原发癌灶表现为等位基因保留而在相应转移灶则为缺失。结论膀胱癌在原发癌及相应转移灶遗传组成上有相当一致性;当转移癌的原发癌不能确定来源时,这些位点的杂合性缺失(LOH)可作为膀胱癌的标志物。Objective To better understand the genetic basis of bladder cancer progression. Methods The study examined the patterns of allelic loss with polymorphic microsatellite markers on chromosomes 9p21 （D9S161, D9S171, IFNA）, regions of putative tumor suppressor gene pl6, and on chromosome 17p13 （TP53）, the p53 locus, in matched primary and metastatic bladder cancers in 18 patients. All patients underwent cystectomy for bladder cancer and were found to have regional lymph node metastases at the time of surgery. Genomic DNA was obtained from primary cancers and matched synchronous lymph node metastases using a microdissection method. Results The overall frequencies of allelic loss were 78% in primary cancers and 89% in paired metastatic cancers. The frequencies of allelic loss in the primary cancers were 86% with D9S161,67% with D9S171,71% with IFNA, and 80% with TP53. The frequencies of allelic loss in matched metastatic cancers were 100% with D9S161, 62% with D9S171, 71% with IFNA, and 80% with TP53. An identical pattern of allelic imbalance （allelic loss or retention） at multiple DNA loci was observed in matched primary and metastatic carcinomas in 16（88% ） cases. Two case showed allelic loss in the metastases, but not in the primary cancers. Conduslon The patterns of allelic loss at chromosomes 9p21 （p16） and 17p13 （p53） are generally maintained during cancer progression to metastasis, and identical allelic loss in primary cancers is conserved in paired metastatic carcinomas. These data suggest that these genetic changes may be useful in establishing a diagnosis and determining tumor origins in difficult cases.

关 键 词：膀胱癌 转移 显微切割 肿瘤进展 

分 类 号：R737.14[医药卫生—肿瘤]