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

Prostate. 2009 Jul 1;69(10):1091-100. doi: 10.1002/pros.20959.


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. We used 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / secondary
  • Aged
  • Cell Line, Tumor
  • Cohort Studies
  • Comparative Genomic Hybridization / methods*
  • Gene Deletion
  • Gene Expression Profiling / methods
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis / methods*
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics*
  • Risk Factors