膀胱癌演变过程中等位基因缺失研究(英文)  

Allelic loss in bladder cancer

作　　者：李光[1] 张海峰[2] 路喜安[2] 

机构地区：[1]首都医科大学附属北京天坛医院病理科,北京100050 [2]山西医科大学第一临床医学院病理科

出　　处：《山西医科大学学报》2008年第8期701-704,共4页Journal of Shanxi Medical University

摘　　要：目的探讨膀胱癌克隆演变(clonal evolution)过程中遗传学机制。方法分别利用4个位于染色体9p21区和17p13区上的具有多态性的微卫星标记物分析18例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分别为78%(14/18)和89%(16/18);原发癌和转移灶在各位点D9S161的缺失频率为86%和100%,D9S171为67%和67%,IFNA71%和71%,TP5380%和80%。在18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例原发癌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,位点D9S161,D9S171,IFNA和TP53的杂合性缺失可能作为膀胱癌的标志物。Objective To better understand the genetic basis of bladder c2.ncer progression. Methods The patterns of allelic loss with polymorphic microsatellite markers on chromosome 9p21 （D9S161, D9S171, IFNA）, regions of putative tumor suppressor gene pl6,and the p53 locus on chromosome 17p13（TP53） ,in matched primary and metastatic bladder cancers from 18 patients were examined. All patients underwent cystectomy,and were found regional lymph node metastases during surgery. Genomic DNA was prepared from primary cancers and matched synchronous lymph node metastases using a microdissection method. Results The overall frequencies of allelic loss were 78 % in primary cancer and 89 % in paired metastatic cancer. The frequencies of allelic loss in primary cancer were 86 % with D9S161,67 % with D9S171,71% with IFNA, and 80 % with TP53. The frequencies of allelic loss in matched metastatic cancer were 100 % with D9S161,67 % 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 carcinoma in 16 cases （88 % ）. Two patients showed allelic loss in the metastasis, but not in primary cancer. Conclusion The pattern of allelic loss at chromosome 9p21 （p16） and 17p13 （p53） is generally maintained during cancer progression to metastasis, and identical allelic loss in primary cancer is conserved in paired metastatic carcinoma. These data suggest that loss of heterozygosity of locus D9S161, D9S171, IFNA and TP53 may be useful targets for diagnosing and determining tumor origins.

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]