title: Target genes of recurrent chromosomal amplification and deletion in urothelial carcinoma.
abstract: BACKGROUND
  Urothelial carcinoma (UC) is characterized by multiple recurrent chromosomal changes on a background of increasing genomic instability. To define target genes of recurrent deletions and amplifications, we explored which gene alterations are common in UC, in two recently established cell lines, BC44 and BC61.
  
  
  METHODS
  Genes located in regions of gain or deletion in the cell lines were identified by array comparative genomic hybridization (aCGH). Six published microarray datasets were analyzed for genes differentially expressed between urothelial tumor vs. normal tissues. Gene expression and chromosomal changes were compared in BC61 cells.
  
  
  RESULTS
  The cell lines share homozygous deletions at 9p21 around CDKN2A and amplifications at 11q13.2 around CCND1. In both cell lines 11 genes were commonly lost and 115 gained. Across UC in general, 230 genes were expressed stronger and 349 weaker; a subset displaying corresponding genetic changes in the cell lines. The commonly affected subset contains well-investigated genes like E2F1 and CCNE1, but also several genes not yet sufficiently investigated in UC.
  
  
  CONCLUSIONS
  Our approach highlights genes involved in cell cycle regulation, apoptosis and signal transduction as commonly deregulated across UC. Nevertheless, many chromosomal regions undergoing recurrent changes harbor several commonly deregulated genes that may act jointly in UC development and progression.
authors: Urologische Klinik, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors: Merlin
authors: M
authors: Weilandt
authors: Urologische Klinik, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors: Annemarie
authors: A
authors: Koch
authors: Institut für Humangenetik, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors: Harald
authors: H
authors: Rieder
authors: Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors: René
authors: R
authors: Deenen
authors: Lehrstuhl für Mathematische Optimierung, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors: Holger
authors: H
authors: Schwender
authors: Urologische Klinik, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors: Günter
authors: G
authors: Niegisch
authors: Urologische Klinik, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors: Wolfgang A
authors: WA
authors: Schulz
mesh_terms: D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D055028:Comparative Genomic Hybridization; D019295:Computational Biology / Q000379:methods; D066264:Datasets as Topic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics / Q000379:methods; D005838:Genotype; D006801:Humans; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
keywords: Urothelial carcinoma; array-CGH; chromosomal gains; chromosomal losses; gene expression microarray