Identification of prefoldin amplification (1q23.3-q24.1) in bladder cancer using comparative genomic hybridization (CGH) arrays of urinary DNA
Open Access
- 1 August 2013
- journal article
- Published by Springer Science and Business Media LLC in Journal of Translational Medicine
- Vol. 11 (1), 182
- https://doi.org/10.1186/1479-5876-11-182
Abstract
Background Array-CGH represents a comprehensive tool to discover genomic disease alterations that could potentially be applied to body fluids. In this report, we aimed at applying array-CGH to urinary samples to characterize bladder cancer. Methods Urinary DNA from bladder cancer patients and controls were hybridized on 44K oligonucleotide arrays. Validation analyses of identified regions and candidates included fluorescent in situ hybridization (FISH) and immunohistochemistry in an independent set of bladder tumors spotted on custom-made tissue arrays (n = 181). Results Quality control of array-CGH provided high reproducibility in dilution experiments and when comparing reference pools. The most frequent genomic alterations (minimal recurrent regions) among bladder cancer urinary specimens included gains at 1q and 5p, and losses at 10p and 11p. Supervised hierarchical clustering identified the gain at 1q23.3-q24.1 significantly correlated to stage (p = 0.011), and grade (p = 0.002). The amplification and overexpression of Prefoldin (PFND2), a selected candidate mapping to 1q23.3-q24.1, correlated to increasing stage and tumor grade by means of custom-designed and optimized FISH (p = 0.013 and p = 0.023, respectively), and immunohistochemistry (p ≤0.0005 and p = 0.011, respectively), in an independent set of bladder tumors included in tissue arrays. Moreover, PFND2 overexpression was significantly associated with poor disease-specific survival (p ≤0.0005). PFND2 was amplified and overexpressed in bladder tumors belonging to patients providing urinary specimens where 1q23.3q24.1 amplification was detected by array-CGH. Conclusions Genomic profiles of urinary DNA mirrowed bladder tumors. Molecular profiling of urinary DNA using array-CGH contributed to further characterize genomic alterations involved in bladder cancer progression. PFND2 was identified as a tumor stratification and clinical outcome prognostic biomarker for bladder cancer patients.This publication has 54 references indexed in Scilit:
- Cancer statistics, 2012CA: A Cancer Journal for Clinicians, 2012
- Fibroblast Growth Factor Receptor 3 Mutations in Bladder Tumors Correlate with Low Frequency of Chromosome AlterationsNeoplasia, 2008
- Application of multiplex FISH, CGH and MSSCP techniques for cytogenetic and molecular analysis of transitional cell carcinoma (TCC) cells in voided urine specimensJournal of Applied Genetics, 2006
- Bladder cancer: Epidemiology, staging and grading, and diagnosisUrology, 2005
- Frequent genetic alterations in flat urothelial hyperplasias and concomitant papillary bladder cancer as detected by CGH, LOH, and FISH analysesThe Journal of Pathology, 2002
- DNA Copy Number Changes in Schistosoma-Associated and Non-Schistosoma-Associated Bladder CancerThe American Journal of Pathology, 2000
- High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarraysNature Genetics, 1998
- Detection of chromosomal imbalances in transitional cell carcinoma of the bladder by comparative genomic hybridization.1995
- Identification of gains and losses of DNA sequences in primary bladder cancer by comparative genomic hybridizationGenes, Chromosomes and Cancer, 1995
- Comparative Genomic Hybridization for Molecular Cytogenetic Analysis of Solid TumorsScience, 1992