High-resolution analysis of genomic alteration on chromosome arm 8p in urothelial carcinoma.
Loss of chromosome arm 8p, sometimes in combination with amplification of proximal 8p, is found in urothelial carcinoma (UC) and other epithelial cancers and is associated with more advanced tumor stage. We carried out array comparative genomic hybridization on 174 UC and 33 UC cell lines to examine breakpoints and copy number. This was followed by a detailed analysis of the cell lines using fluorescence in situ hybridization (FISH) and, in some cases, M-FISH, to refine breakpoints and determine translocation partners, heterozygosity analysis, and analysis of expression of selected genes. We showed an overall pattern of 8p loss with reduced heterozygosity and reduced gene expression. Amplification was seen in some samples and shown in the cell line JMSU1 to correlate with overexpression of ZNF703, ERLIN2, PROSC, GPR124, and BRF2. Apart from the centromere, no single breakpoint was overrepresented, and we postulate that frequent complex changes without consistent breakpoints reflect the need for alterations of combinations of genes. The region around 2 Mb, which was homozygously deleted in one cell line and includes the gene ARHGEF10 and the micro-RNA hsa-mir-596, is one candidate tumor suppressor gene region.
Williams
Sarah V
SV
Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK.
Platt
Fiona M
FM
Hurst
Carolyn D
CD
Aveyard
Jo S
JS
Taylor
Claire F
CF
Pole
Jessica C M
JC
Garcia
Maria J
MJ
Knowles
Margaret A
MA
D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8; D056915:DNA Copy Number Variations; D005784:Gene Amplification; D006801:Humans; D019656:Loss of Heterozygosity; D001749:Urinary Bladder Neoplasms / Q000235:genetics*