Genetic markers associated with early cancer-specific mortality following prostatectomy
Article first published online: 22 APR 2013
Copyright © 2013 American Cancer Society
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Liu, W., Xie, C. C., Thomas, C. Y., Kim, S.-T., Lindberg, J., Egevad, L., Wang, Z., Zhang, Z., Sun, J., Sun, J., Koty, P. P., Kader, A. K., Cramer, S. D., Bova, G. S., Zheng, S. L., Grönberg, H., Isaacs, W. B. and Xu, J. (2013), Genetic markers associated with early cancer-specific mortality following prostatectomy. Cancer. doi: 10.1002/cncr.27954
- Article first published online: 22 APR 2013
- Manuscript Accepted: 27 NOV 2012
- Manuscript Revised: 20 NOV 2012
- Manuscript Received: 24 AUG 2012
- National Institutes of Health. Grant Numbers: CA106523, CA95052, and CA105055, CA133066, and CA135008
- Department of Defense. Grant Number: PC051264
- prostate cancer death;
- somatic DNA copy number
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.
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.
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.
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;. © 2013 American Cancer Society.