Bladder cancer stage and outcome by array-based comparative genomic hybridization

Ekaterini Blaveri, Jeremy L. Brewer, Ritu Roydasgupta, Jane Fridlyand, Sandy Devries, Theresa Koppie, Sunanda Pejavar, Kshama Mehta, Peter Carroll, Jeff P. Simko, Frederic M. Waldman

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

Purpose: Bladder carcinogenesis is believed to follow alternative pathways of disease progression driven by an accumulation of genetic alterations. The purpose of this study was to evaluate associations between measures of genomic instability and bladder cancer clinical phenotype. Experimental Design: Genome-wide copy number profiles were obtained for 98 bladder tumors of diverse stages (29 pTa, 14 PT1, 55 pT2-4) and grades (21 low-grade and 8 high-grade superficial tumors) by array-based comparative genomic hybridization (CGH). Each array contained 2,464 bacterial artificial chromosome and P1 clones, providing an average resolution of 1.5 Mb across the genome. A total of 54 muscle-invasive cases had follow-up information available. Overall outcome analysis was done for patients with muscle-invasive tumors having "good" (alive >2 years) versus "bad" (dead in a versus pT1, P = 0.0003; pTa versus pT2-4, P = 0.02; and pT1 versus pT2-4, P = 0.03). Individual clones that differed significantly between different tumor stages were identified after adjustment for multiple comparisons (false discovery rate <0.05). For muscle-invasive tumors, the FGA was associated with patient outcome (bad versus good prognosis patients, P = 0.002) and was identified as the only independent predictor of overall outcome based on a multivariate Cox proportional hazards method. Unsupervised hierarchical clustering separated "good" and "bad" prognosis muscle-invasive tumors into clusters that showed significant association with FGA and survival (Kaplan-Meier, P = 0.019). Supervised tumor classification (prediction analysis for microarrays) had a 71% classification success rate based on 102 unique clones. Conclusions: Array-based CGH identified quantitative and qualitative differences in DNA copy number alterations at high resolution according to tumor stage and grade. Fraction genome altered was associated with worse outcome in muscle-invasive tumors, independent of other clinicopathologic parameters. Measures of genomic instability add independent power to outcome prediction of bladder tumors.

Original languageEnglish (US)
Pages (from-to)7012-7022
Number of pages11
JournalClinical Cancer Research
Volume11
Issue number19 I
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

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Comparative Genomic Hybridization
Urinary Bladder Neoplasms
Neoplasms
Muscles
Clone Cells
Genomic Instability
Genome
Bacterial Artificial Chromosomes
Microarray Analysis
Cluster Analysis
Disease Progression
Carcinogenesis
Urinary Bladder
Research Design
Phenotype
Survival
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Blaveri, E., Brewer, J. L., Roydasgupta, R., Fridlyand, J., Devries, S., Koppie, T., ... Waldman, F. M. (2005). Bladder cancer stage and outcome by array-based comparative genomic hybridization. Clinical Cancer Research, 11(19 I), 7012-7022. https://doi.org/10.1158/1078-0432.CCR-05-0177

Bladder cancer stage and outcome by array-based comparative genomic hybridization. / Blaveri, Ekaterini; Brewer, Jeremy L.; Roydasgupta, Ritu; Fridlyand, Jane; Devries, Sandy; Koppie, Theresa; Pejavar, Sunanda; Mehta, Kshama; Carroll, Peter; Simko, Jeff P.; Waldman, Frederic M.

In: Clinical Cancer Research, Vol. 11, No. 19 I, 01.10.2005, p. 7012-7022.

Research output: Contribution to journalArticle

Blaveri, E, Brewer, JL, Roydasgupta, R, Fridlyand, J, Devries, S, Koppie, T, Pejavar, S, Mehta, K, Carroll, P, Simko, JP & Waldman, FM 2005, 'Bladder cancer stage and outcome by array-based comparative genomic hybridization', Clinical Cancer Research, vol. 11, no. 19 I, pp. 7012-7022. https://doi.org/10.1158/1078-0432.CCR-05-0177
Blaveri E, Brewer JL, Roydasgupta R, Fridlyand J, Devries S, Koppie T et al. Bladder cancer stage and outcome by array-based comparative genomic hybridization. Clinical Cancer Research. 2005 Oct 1;11(19 I):7012-7022. https://doi.org/10.1158/1078-0432.CCR-05-0177
Blaveri, Ekaterini ; Brewer, Jeremy L. ; Roydasgupta, Ritu ; Fridlyand, Jane ; Devries, Sandy ; Koppie, Theresa ; Pejavar, Sunanda ; Mehta, Kshama ; Carroll, Peter ; Simko, Jeff P. ; Waldman, Frederic M. / Bladder cancer stage and outcome by array-based comparative genomic hybridization. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 19 I. pp. 7012-7022.
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AU - Devries, Sandy

AU - Koppie, Theresa

AU - Pejavar, Sunanda

AU - Mehta, Kshama

AU - Carroll, Peter

AU - Simko, Jeff P.

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