High-resolution array CGH identifies novel regions of genomic alteration in intermediate-risk prostate cancer.
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.
Department of Radiation Oncology, University of Toronto and Radiation Medicine Program, Princess Margaret Hospital-University Health Network, Toronto, Ontario, Canada.
Adrian S
AS
Ishkanian
Chad A
CA
Mallof
James
J
Ho
Alice
A
Meng
Monique
M
Albert
Amena
A
Syed
Theodorus
T
van der Kwast
Michael
M
Milosevic
Maisa
M
Yoshimoto
Jeremy A
JA
Squire
Wan L
WL
Lam
Robert G
RG
Bristow
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000556:secondary; D000368:Aged; D045744:Cell Line, Tumor; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization / Q000379:methods*; D017353:Gene Deletion; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D012307:Risk Factors