High-resolution analysis of genomic copy number alterations in bladder cancer by microarray-based comparative genomic hybridization
High-resolution analysis of genomic copy number alterations in bladder cancer by microarray-based comparative genomic hybridization
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DOI：
10.1038/sj.onc.1207260
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发表时间：
2004-03-18
期刊：
影响因子：
8
通讯作者：
Knowles, MA
中科院分区：
文献类型：
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作者：
Hurst, CD;Fiegler, H;Knowles, MA
我们使用阵列比较基因组杂交（CGH）筛选了22个膀胱肿瘤衍生细胞系和一个正常尿路上皮衍生细胞系的全基因组拷贝数变化。阵列CGH与现有的多重荧光原位杂交（M-FISH）结果的比较显示出良好的一致性。通过阵列CGH更准确地定义了获得和丢失的区域，并且检测到几个M-FISH未鉴定的小缺失区域。许多遗传变化被确定，其中许多是兼容的传统CGH和杂合性丢失分析膀胱肿瘤的先前结果。最常见的变化是4 q完全或部分丢失（83%）和20 q增加（78%）。其他常见的丢失是18 q（65%），8 p（65%），2 q（61%），6 q（61%），3 p（56%），13 q（56%），4p（52%），6p（52%），10 p（52%），10 q（52%）和5 p（43%）。我们已经改进了在8p21.2- p21.3的缺失区域的定位到约1 Mb的间隔。五个肿瘤抑制基因的纯合缺失得到证实，并确定了几个潜在的新的纯合缺失。总共检测到15个高水平扩增，其中先前报道的在6p22.3的扩增是最常见的。真实的-时间PCR分析揭示了一种新的候选基因，其在所有细胞系中具有一致的过表达，具有6p22.3扩增子。
We have screened 22 bladder tumour- derived cell lines and one normal urothelium- derived cell line for genome- wide copy number changes using array comparative genomic hybridization ( CGH). Comparison of array CGH with existing multiplex-fluorescence in situ hybridization ( M-FISH) results revealed excellent concordance. Regions of gain and loss were defined more accurately by array CGH, and several small regions of deletion were detected that were not identified by M- FISH. Numerous genetic changes were identified, many of which were compatible with previous results from conventional CGH and loss of heterozygosity analyses on bladder tumours. The most frequent changes involved complete or partial loss of 4q ( 83%) and gain of 20q ( 78%). Other frequent losses were of 18q ( 65%), 8p ( 65%), 2q ( 61%), 6q ( 61%), 3p ( 56%), 13q ( 56%), 4p ( 52%), 6p ( 52%), 10p ( 52%), 10q ( 52%) and 5p ( 43%). We have refined the localization of a region of deletion at 8p21.2- p21.3 to an interval of approximately 1 Mb. Five homozygous deletions of tumour suppressor genes were confirmed, and several potentially novel homozygous deletions were identified. In all, 15 high- level amplifications were detected, with a previously reported amplification at 6p22.3 being the most frequent. Real- time PCR analysis revealed a novel candidate gene with consistent overexpression in all cell lines with the 6p22.3 amplicon.