膀胱癌组织中染色体3q26．1小片段高频率缺失及其意义  

The significance of loss of 3q26. 1 small fragment in urothelial carcinoma of th bladder

作　　者：郑阳[1] 寿建忠[2] 蔡雄伟[1] 郑闪[3] 刘宇[1] 毕新刚[2] 柏景乔[1] 高燕宁[1] 

机构地区：[1]中国医学科学院北京协和医学院肿瘤医院肿瘤研究所,"癌发生及预防分子机理"北京市重点实验室,100021 [2]中国医学科学院北京协和医学院泌尿外科,100021 [3]中国医学科学院北京协和医学院肿瘤医院病理科,100021

出　　处：《中华泌尿外科杂志》2011年第4期223-227,共5页Chinese Journal of Urology

基　　金：国家自然科学基金（30870984）;中央级公益性科研院所基本科研业务费专项课题（JK2006B06）

摘　　要：目的探讨人膀胱尿路上皮癌组织中染色体3q26．1小片段拷贝数改变及其临床意义。方法采用微阵列比较基因组杂交（array comparative genomic hybridization，Array—CGH）技术分析35例膀胱癌组织（Ta～T1 18例，T2～T4 17例）基因组DNA（区段／基因）拷贝数改变。采用实时荧光定量PCR验证57例冻存膀胱癌组织（Ta～T1 25例，T2～T4 32例），34例甲醛固定石蜡包埋膀胱癌组织（Ta～T1 15例，T2～T4 19例），以及29例膀胱癌患者术前尿脱落细胞和15例健康志愿者尿脱落细胞中3q26．1小片段拷贝数的改变情况。结果Array-CGH分析显示，膀胱癌组织中存在染色体3q26．1中一个小片段的高频率缺失，缺失率为77．1％（27／35）。实时荧光定量PCR验证发现，57例膀胱癌冻存组织和34例膀胱癌固定包埋组织中该3q26．1小片段高频率缺失率分别为78．9％（45／57）和100．0％（34／34）；膀胱癌患者术前尿脱落细胞中3q26．1小片段的相对拷贝数（中位数为0．0020）与正常对照组（中位数为0．0030）相比差异有统计学意义（P〈0．01）。结论染色体3q26．1小片段缺失是膀胱尿路上皮癌特征性的DNA分子水平异常改变。尿脱落细胞的3q26．1小片段缺失有可能成为膀胱癌的分子标志物。Objective To investigate the copy number changes on chromosome 3q26. 1 in urothelial carcinoma of the bladder, and to explore its potential clinical significance. Methods The microarray based comparative genomic hybridization （Array CGH） approach was used to analyze the genome-wide copy number changes of 35 tumor tissue samples of bladder cancer. To confirm the loss of a small fragment in 3q26. 1 detected by Array-CGH, real time fluorescent quantitative polymerase chain reaction （real time PCR） was performed with 57 frozen tumor tissue samples and 34 formalinfixed paraffin-embedded （FFPE） tumor tissue samples. The urine sediment cells collected from 15 healthy volunteers and 29 bladder cancer patients were checked as above. Results The Array CGH data showed that the copy number loss of a small fragment in 3q26.1 was detected in 77.1% （27/35） of the tumor tissue samples investigated. Real time PCR analysis validated this loss of a small frag ment of 3q26.1 with high frequencies in both 57 frozen tumor samples and 34 FFPE tumor samples. The percentage of samples exbibiting loss was 78. 9%（45/57） and 100. 0% （3/1/34） respectively. Furthermore, the relative copy number of the 3q26.1 small fragment was significantly lower in the urinary sediment cells of the patients （median=0. 0020）, comparing with that of healthy controls （median 0. 0030） （P〈0.01）. Conclusions Loss of the small fragment in 3q26.1 could be a characteris tic genetic change of urothelial carcinoma of the bladder. It may serve as a potential molecular marker for bladder cancer.

关 键 词：膀胱肿瘤 癌 DNA探针 肿瘤标记 生物学 DNA拷贝数 

分 类 号：R737.14[医药卫生—肿瘤]