High-resolution array CGH identifies novel regions of genomic alteration in intermediate-risk prostate cancer

Adrian S. Ishkanian, Chad A. Mallof, James Ho, Alice Meng, Monique Albert, Amena Syed, Theodorus Van Der Kwast, Michael Milosevic, Maisa Yoshimoto, Jeremy A. Squire, Wan L. Lam, Robert G. Bristow

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71 Scopus citations

Abstract

Approximately one-third of prostate cancer patients present with intermediate risk disease. Interestingly, while this risk group is clinically well defined, it demonstrates the most significant heterogeneity in PSA-based biochemical outcome. Further, the majority of candidate genes associated with prostate cancer progression have been identified using cell lines, xenograft models, and high-risk androgen-independent or metastatic patient samples.Weused a global high-resolution array comparative genomic hybridization (CGH) assay to characterize copy number alterations (CNAs) in intermediate risk prostate cancer. Herein, we show this risk group contains a number of alterations previously associated with high-risk disease: (1) deletions at 21q22.2 (TMPRSS2:ERG), 16q22-24 (containing CDH1), 13q14.2 (RB1), 10q23.31 (PTEN), 8p21 (NKX3.1); and, (2) amplification at 8q21.3-24.3 (containing c-MYC). In addition, we identified six novel microdeletions at high frequency: 1q42.12-q42.3 (33.3%), 5q12.3-13.3 (21%), 20q13.32-13.33 (29.2%), 22q11.21 (25%), 22q12.1 (29.2%), and 22q13.31 (33.3%). Further, we show there is little concordance between CNAs from these clinical samples and those found in commonly used prostate cancer cell models. These unexpected findings suggest that the intermediate-risk category is a crucial cohort warranting further study to determine if a unique molecular fingerprint can predict aggressive versus indolent phenotypes.

Original languageEnglish (US)
Pages (from-to)1091-1100
Number of pages10
JournalProstate
Volume69
Issue number10
DOIs
StatePublished - Jul 1 2009

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Keywords

  • Array-comparative genomic hybridization
  • Biopsies
  • DNA
  • Genomics
  • Intermediate risk prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Ishkanian, A. S., Mallof, C. A., Ho, J., Meng, A., Albert, M., Syed, A., Van Der Kwast, T., Milosevic, M., Yoshimoto, M., Squire, J. A., Lam, W. L., & Bristow, R. G. (2009). High-resolution array CGH identifies novel regions of genomic alteration in intermediate-risk prostate cancer. Prostate, 69(10), 1091-1100. https://doi.org/10.1002/pros.20959