Array-based comparative genomic hybridization for genome-wide screening of DNA copy number in bladder tumors.
Array-based comparative genomic hybridization for genome-wide screening of DNA copy number in bladder tumors.
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发表时间：
2003-06
期刊：
影响因子：
11.2
通讯作者：
J. Veltman;J. Fridlyand;Sunanda Pejavar;A. Olshen;J. Korkola;S. Devries;P. Carroll;W. Kuo;D. Pinkel;D. Albertson;C. Cordon-Cardo;Ajay N. Jain;F. Waldman
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作者：
J. Veltman;J. Fridlyand;Sunanda Pejavar;A. Olshen;J. Korkola;S. Devries;P. Carroll;W. Kuo;D. Pinkel;D. Albertson;C. Cordon-Cardo;Ajay N. Jain;F. Waldman
使用基于阵列的比较基因组杂交（阵列CGH），在41个原发性膀胱肿瘤的全基因组拷贝数的特点。除了先前在大的染色体区域中鉴定的改变之外，在许多小的基因组区域中鉴定了改变，其中一些具有高水平扩增或纯合缺失。在192个基因组克隆中检测到高水平扩增，最常见的是6p22.3（E2 F3），8 p12（FGFR 1），8q22.2（CMYC），11 q13（CCND 1，EMS 1，INT 2）和19q13.1（CCNE）。在51个基因组克隆中检测到纯合缺失，其中4个在1个以上病例中显示缺失：2个克隆定位于9p21.3（9例中为CDKN 2A/p16），1个定位于8p23.1（3例），1个定位于11 p13（2例）。CCNE 1的拷贝数增加与ERBB 2的增加之间以及CCND 1的增加与TP 53的缺失之间存在显著相关性。此外，CCND 1的增加与E2 F3的增加之间存在显著的互补关联。尽管拷贝数变化与肿瘤分期或分级之间没有显著关系，但基因组位点之间的相关行为表明，阵列CGH在理解膀胱肿瘤生物学关键途径方面将变得越来越重要。
Genome-wide copy number profiles were characterized in 41 primary bladder tumors using array-based comparative genomic hybridization (array CGH). In addition to previously identified alterations in large chromosomal regions, alterations were identified in many small genomic regions, some with high-level amplifications or homozygous deletions. High-level amplifications were detected for 192 genomic clones, most frequently at 6p22.3 (E2F3), 8p12 (FGFR1), 8q22.2 (CMYC), 11q13 (CCND1, EMS1, INT2), and 19q13.1 (CCNE). Homozygous deletions were detected in 51 genomic clones, with four showing deletions in more than one case: two clones mapping to 9p21.3 (CDKN2A/p16, in nine cases), one at 8p23.1 (three cases), and one at 11p13 (two cases). Significant correlations were observed between copy number gain of clones containing CCNE1 and gain of ERBB2, and between gain of CCND1 and deletion of TP53. In addition, there was a significant complementary association between gain of CCND1 and gain of E2F3. Although there was no significant relationship between copy number changes and tumor stage or grade, the linked behavior among genomic loci suggests that array CGH will be increasingly important in understanding pathways critical to bladder tumor biology.