Journal of Probability and Statistics
Volume 2012 (2012), Article ID 873570, 19 pages
Research Article

Clustering-Based Method for Developing a Genomic Copy Number Alteration Signature for Predicting the Metastatic Potential of Prostate Cancer

1Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2Human Genetics Program, Department of Pediatrics, NYU Langone Medical Center, New York, NY 10016, USA
3Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
4Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
5Department of Pathology, NYU Langone Medical Center, New York, NY 10016, USA
6Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
7NYU Cancer Institute and Department of Microbiology, NYU Langone Medical Center, New York, NY 10016, USA

Received 1 March 2012; Revised 17 May 2012; Accepted 31 May 2012

Academic Editor: Xiaohua Douglas Zhang

Copyright © 2012 Alexander Pearlman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The transition of cancer from a localized tumor to a distant metastasis is not well understood for prostate and many other cancers, partly, because of the scarcity of tumor samples, especially metastases, from cancer patients with long-term clinical follow-up. To overcome this limitation, we developed a semi-supervised clustering method using the tumor genomic DNA copy number alterations to classify each patient into inferred clinical outcome groups of metastatic potential. Our data set was comprised of 294 primary tumors and 49 metastases from 5 independent cohorts of prostate cancer patients. The alterations were modeled based on Darwin’s evolutionary selection theory and the genes overlapping these altered genomic regions were used to develop a metastatic potential score for a prostate cancer primary tumor. The function of the proteins encoded by some of the predictor genes promote escape from anoikis, a pathway of apoptosis, deregulated in metastases. We evaluated the metastatic potential score with other clinical predictors available at diagnosis using a Cox proportional hazards model and show our proposed score was the only significant predictor of metastasis free survival. The metastasis gene signature and associated score could be applied directly to copy number alteration profiles from patient biopsies positive for prostate cancer.