title: Genetic markers associated with early cancer-specific mortality following prostatectomy.
abstract: BACKGROUND
  This study sought to identify novel effectors and markers of localized but potentially life-threatening prostate cancer (PCa), by evaluating chromosomal copy number alterations (CNAs) in tumors from patients who underwent prostatectomy and correlating these with clinicopathologic features and outcome.
  
  
  METHODS
  CNAs in tumor DNA samples from 125 patients in the discovery cohort who underwent prostatectomy were assayed with high-resolution Affymetrix 6.0 single-nucleotide polymorphism microarrays and then analyzed using the Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm.
  
  
  RESULTS
  The assays revealed 20 significant regions of CNAs, 4 of them novel, and identified the target genes of 4 of the alterations. By univariate analysis, 7 CNAs were significantly associated with early PCa-specific mortality. These included gains of chromosomal regions that contain the genes MYC, ADAR, or TPD52 and losses of sequences that incorporate SERPINB5, USP10, PTEN, or TP53. On multivariate analysis, only the CNAs of PTEN (phosphatase and tensin homolog) and MYC (v-myc myelocytomatosis viral oncogene homolog) contributed additional prognostic information independent of that provided by pathologic stage, Gleason score, and initial prostate-specific antigen level. Patients whose tumors had alterations of both genes had a markedly elevated risk of PCa-specific mortality (odds ratio = 53; 95% CI = 6.92-405, P = 1 × 10(-4)). Analyses of 333 tumors from 3 additional distinct patient cohorts confirmed the relationship between CNAs of PTEN and MYC and lethal PCa.
  
  
  CONCLUSIONS
  This study identified new CNAs and genes that likely contribute to the pathogenesis of localized PCa and suggests that patients whose tumors have acquired CNAs of PTEN, MYC, or both have an increased risk of early PCa-specific mortality.
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Wennuan
authors.initials: W
authors.lastname: Liu
authors.forename: Chunmei C
authors.initials: CC
authors.lastname: Xie
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Thomas
authors.forename: Seong-Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Johan
authors.initials: J
authors.lastname: Lindberg
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jishan
authors.initials: J
authors.lastname: Sun
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Koty
authors.forename: A Karim
authors.initials: AK
authors.lastname: Kader
authors.forename: Scott D
authors.initials: SD
authors.lastname: Cramer
authors.forename: G Steven
authors.initials: GS
authors.lastname: Bova
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D056915:DNA Copy Number Variations; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D011519:Proto-Oncogenes / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D017430:Prostate-Specific Antigen