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High‐resolution array CGH identifies novel regions of genomic alteration in intermediate‐risk prostate cancer
Author(s) -
Ishkanian Adrian S.,
Mallof Chad A.,
Ho James,
Meng Alice,
Albert Monique,
Syed Amena,
van der Kwast Theodorus,
Milosevic Michael,
Yoshimoto Maisa,
Squire Jeremy A.,
Lam Wan L.,
Bristow Robert G.
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20959
Subject(s) - prostate cancer , pten , prostate , tmprss2 , concordance , comparative genomic hybridization , chromoplexy , cancer , oncology , cancer research , biology , medicine , disease , genetics , pca3 , gene , chromosome , apoptosis , covid-19 , pi3k/akt/mtor pathway , infectious disease (medical specialty)
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. Prostate 69:1091–1100, 2009. © 2009 Wiley‐Liss, Inc.