Genetic markers associated with early cancer‐specific mortality following prostatectomy. Issue 13 (22nd April 2013)

• Record Type: Journal Article
• Authors: Liu, Wennuan; Xie, Chunmei C.; Thomas, Christopher Y.; Kim, Seong‐Tae; 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
• Is Part Of: Cancer. Volume 119:Issue 13(2013)
• Page Start: 2405
• Page End: 2412
• Publication Date: 2013-04-22
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.27954
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr27954-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>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.</p> </sec> <sec id="cncr27954-sec-0002" sec-type="section"> <title>METHODS</title> <p>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.</p> </sec> <sec id="cncr27954-sec-0003" sec-type="section"> <title>RESULTS</title> <p>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 <italic>MYC</italic>, <italic>ADAR</italic>, or <italic>TPD52</italic> and losses of sequences that incorporate <italic>SERPINB5</italic>, <italic>USP10</italic>, <italic>PTEN</italic>, or <italic>TP53</italic>. On multivariate analysis, only the CNAs of <italic>PTEN</italic> (phosphatase and tensin homolog) and <italic>MYC</italic> (v‐<italic>myc</italic> 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, <italic>P</italic> = 1 × 10<sup>−4</sup>). Analyses of 333 tumors from 3 additional distinct patient cohorts confirmed the relationship between CNAs of <italic>PTEN</italic> and <italic>MYC</italic> and lethal PCa.</p> </sec> <sec id="cncr27954-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>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 <italic>PTEN</italic>, <italic>MYC</italic>, or both have an increased risk of early PCa‐specific mortality. <bold><italic>Cancer</italic> 2013;119:2405‐2412</bold>. © <italic>2013 American Cancer Society</italic>.</p> </sec> </abstract>