CAJ | 학술논문

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～T118例,T2～T417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～T125例,T2～T4 32例),34例甲醛固定石蜡包埋膀胱癌组织(Ta～T115例,T2～T419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.
목적 탐토인방광뇨로상피암조직중염색체3q26.1소편단고패수개변급기림상의의.방법 채용미진렬비교기인조잡교(array comparative genomic hybridization,Array-CGH)기술분석35례방광암조직(Ta～T118례,T2～T417례)기인조DNA(구단/기인)고패수개변.채용실시형광정량PCR험증57례동존방광암조직(Ta～T125례,T2～T4 32례),34례갑철고정석사포매방광암조직(Ta～T115례,T2～T419례),이급29례방광암환자술전뇨탈락세포화15례건강지원자뇨탈락세포중3q26.1소편단고패수적개변정황.결과 Array-CGH분석현시,방광암조직중존재염색체3q26.1중일개소편단적고빈솔결실,결실솔위77.1%(27/35).실시형광정량PCR험증발현,57례방광암동존조직화34례방광암고정포매조직중해3q26.1소편단고빈솔결실솔분별위78.9%(45/57)화100.0%(34/34);방광암환자술전뇨탈락세포중3q26.1소편단적상대고패수(중위수위0.0020)여정상대조조(중위수위0.0030)상비차이유통계학의의(P＜0.01).결론 염색체3q26.1소편단결실시방광뇨로상피암특정성적DNA분자수평이상개변.뇨탈락세포적3q26.1소편단결실유가능성위방광암적분자표지물.
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 fragment of 3q26.1 with high frequencies in both 57 frozen tumor samples and 34 FFPE tumor samples.The percentage of samples exhibiting loss was 78.9% (45/57) and 100. 0% (34/34) 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 characteristic genetic change of urothelial carcinoma of the bladder. It may serve as a potential molecular marker for bladder cancer.