Genetic markers associated with early cancer-specific mortality following prostatectomy - Liu - 2013 - Cancer - Wiley Online Library

Genetic markers associated with early cancer-specific mortality following prostatectomy - Liu - 2013 - Cancer - Wiley Online Library

Genetic markers associated with early cancer-specific mortality following prostatectomy

1. Wennuan Liu PhD^1,2,


2. Chunmei C. Xie PhD^1,2,


3. Christopher Y. Thomas MD³,


4. Seong-Tae Kim PhD^1,2,


5. Johan Lindberg PhD⁴,


6. Lars Egevad MD⁵,


7. Zhong Wang MS^1,2,


8. Zheng Zhang MS^1,2,


9. Jishan Sun PhD^1,2,


10. Jielin Sun PhD^1,2,


11. Patrick P. Koty PhD^1,2,6,


12. A. Karim Kader MD⁷,


13. Scott D. Cramer PhD⁸,


14. G. Steven Bova MD⁹,


15. S. Lilly Zheng MD^1,2,


16. Henrik Grönberg MD⁴,


17. William B. Isaacs PhD¹⁰,


18. Jianfeng Xu MD, DrPh^1,2,11,*

Article first published online: 22 APR 2013

DOI: 10.1002/cncr.27954

Copyright © 2013 American Cancer Society

Issue

Cancer

Early View (Online Version of Record published before inclusion in an issue)

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How to CiteAuthor InformationPublication HistoryFunding Information

How to Cite

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

Author Information

1. ¹Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina


2. ²Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina


3. ³Department of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina


4. ⁴Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden


5. ⁵Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden


6. ⁶Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina


7. ⁷Department of Surgery, University of California San Diego, San Diego, California


8. ⁸Department of Pharmacology, University of Colorado, Aurora, Colorado


9. ⁹Institute of Biomedical Technology, University of Tampere, Tampere, Finland


10. ¹⁰Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland


11. ¹¹Department of Urology, Wake Forest University School of Medicine, Winston-Salem, North Carolina

^*Corresponding author: Jianfeng Xu, MD, DrPh, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157. E-mail: jxu@wfubmc.edu Fax: (336) 713-7566

Publication History

1. Article first published online: 22 APR 2013


2. Manuscript Accepted: 27 NOV 2012


3. Manuscript Revised: 20 NOV 2012


4. Manuscript Received: 24 AUG 2012

Funded by

• National Institutes of Health. Grant Numbers: CA106523, CA95052, and CA105055, CA133066, and CA135008


• Department of Defense. Grant Number: PC051264

 

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Keywords:

• prostate cancer death;


• PTEN;


• MYC;


• somatic DNA copy number

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;. © 2013 American Cancer Society.