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Updated: Apr 27, 2026
Cell-Free DNA Integrity Analysis in Urine Samples
Published on: January 5, 2017
Target genes of recurrent chromosomal amplification and deletion in urothelial carcinoma
Merlin Weilandt1, Annemarie Koch1, Harald Rieder2
1Urologische Klinik, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
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.
Materials And 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.
Discussion:
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.
Insights
Genomic instability in urothelial carcinoma (UC) involves common gene deletions and amplifications. This study identified key deregulated genes in cell cycle regulation and apoptosis, crucial for UC development.
Area of Science:
- Genomics
- Cancer Biology
- Urothelial Carcinoma Research
Background:
- Urothelial carcinoma (UC) exhibits significant genomic instability with recurrent chromosomal alterations.
- Understanding gene alterations is critical for defining therapeutic targets in UC.
Purpose of the Study:
- To identify common gene deletions and amplifications in urothelial carcinoma.
- To define target genes affected by recurrent genetic changes in UC.
- To analyze gene expression and chromosomal alterations in established UC cell lines (BC44, BC61).
Main Methods:
- Array comparative genomic hybridization (aCGH) to identify gene copy number variations.
- Analysis of six published microarray datasets for differential gene expression in UC tissues.
- Integration of gene expression data with chromosomal changes in BC61 cells.
Main Results:
- Shared homozygous deletions at 9p21 (CDKN2A) and amplifications at 11q13.2 (CCND1) were observed in cell lines.
- Commonly lost: 11 genes; Commonly gained: 115 genes in the cell lines.
- UC tissues showed 230 upregulated and 349 downregulated genes, with a subset overlapping cell line findings, including E2F1 and CCNE1.
Conclusions:
- Deregulated genes in cell cycle regulation, apoptosis, and signal transduction are common in UC.
- Recurrently altered chromosomal regions harbor multiple jointly acting genes in UC pathogenesis.
- The study highlights novel candidate genes for UC investigation.
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