title: Genome abnormalities precede prostate cancer and predict clinical relapse.
abstract: The prediction of prostate cancer clinical outcome remains a major challenge after the diagnosis, even with improved early detection by prostate-specific antigen (PSA) monitoring. To evaluate whether copy number variation (CNV) of the genomes in prostate cancer tumor, in benign prostate tissues adjacent to the tumor (AT), and in the blood of patients with prostate cancer predicts biochemical (PSA) relapse and the kinetics of relapse, 241 samples (104 tumor, 49 matched AT, 85 matched blood, and 3 cell lines) were analyzed using Affymetrix SNP 6.0 chips. By using gene-specific CNV from tumor, the genome model correctly predicted 73% (receiver operating characteristic P = 0.003) cases for relapse and 75% (P < 0.001) cases for short PSA doubling time (PSADT, <4 months). The gene-specific CNV model from AT correctly predicted 67% (P = 0.041) cases for relapse and 77% (P = 0.015) cases for short PSADT. By using median-sized CNV from blood, the genome model correctly predicted 81% (P < 0.001) cases for relapse and 69% (P = 0.001) cases for short PSADT. By using median-sized CNV from tumor, the genome model correctly predicted 75% (P < 0.001) cases for relapse and 80% (P < 0.001) cases for short PSADT. For the first time, our analysis indicates that genomic abnormalities in either benign or malignant tissues are predictive of the clinical outcome of a malignancy.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Yan P
authors.initials: YP
authors.lastname: Yu
authors.forename: Chi
authors.initials: C
authors.lastname: Song
authors.forename: George
authors.initials: G
authors.lastname: Tseng
authors.forename: Bao Guo
authors.initials: BG
authors.lastname: Ren
authors.forename: William
authors.initials: W
authors.lastname: LaFramboise
authors.forename: George
authors.initials: G
authors.lastname: Michalopoulos
authors.forename: Joel
authors.initials: J
authors.lastname: Nelson
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Luo
mesh_terms: D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012008:Recurrence; D012680:Sensitivity and Specificity
chemical_list: D004273:DNA, Neoplasm; D017430:Prostate-Specific Antigen