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Genetic markers associated with early cancer‐specific mortality following prostatectomy
Author(s) -
Liu Wennuan,
Xie Chunmei C.,
Thomas Christopher Y.,
Kim SeongTae,
Lindberg Johan,
Egevad Lars,
Wang Zhong,
Zhang Zheng,
Sun Jishan,
Sun Jielin,
Koty Patrick P.,
Kader A. Karim,
Cramer Scott D.,
Bova G. Steven,
Zheng S. Lilly,
Grönberg Henrik,
Isaacs William B.,
Xu Jianfeng
Publication year - 2013
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.27954
Subject(s) - pten , prostate cancer , prostatectomy , medicine , cancer , oncology , cancer research , biology , genetics , pi3k/akt/mtor pathway , apoptosis
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. Cancer 2013;119:2405‐2412 . © 2013 American Cancer Society .