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Human Molecular Genetics Advance Access originally published online on May 11, 2004
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Human Molecular Genetics, 2004, Vol. 13, No. 13 1303-1313
DOI: 10.1093/hmg/ddh155
Human Molecular Genetics, Vol. 13, No. 13 © Oxford University Press 2004; all rights reserved

Whole genome scanning identifies genotypes associated with recurrence and metastasis in prostate tumors

Pamela L. Paris1, Armann Andaya1, Jane Fridlyand1, Ajay N. Jain1, Vivian Weinberg1, David Kowbel1, John H. Brebner1, Jeff Simko1,2, J.E. Vivienne Watson1, Stas Volik1, Donna G. Albertson1, Daniel Pinkel1, Janneke C. Alers3, Theodorus H. van der Kwast3, Kees J. Vissers3, Fritz H. Schroder4, Mark F. Wildhagen4, Phillip G. Febbo5,8, Arul M. Chinnaiyan6, Kenneth J. Pienta6, Peter R. Carroll7, Mark A. Rubin8, Colin Collins1,* and Herman van Dekken3

1Comprehensive Cancer Center and 2Department of Anatomic Pathology, University of California at San Francisco, San Francisco, CA 94115, USA, 3Department of Pathology and 4Department of Urology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands, 5Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA, 6Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA, 7Department of Urology, Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA 94115, USA and 8Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

Received February 4, 2004; Accepted April 28, 2004

Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm among American males and is the second leading cause of cancer-related death. Prostate specific antigen screening has resulted in earlier disease detection, yet ~30% of men will die of metastatic disease. Slow disease progression, an aging population and associated morbidity and mortality underscore the need for improved disease classification and therapies. To address these issues, we analyzed a cohort of patients using array comparative genomic hybridization (aCGH). The cohort comprises 64 patients, half of whom recurred postoperatively. Analysis of the aCGH profiles revealed numerous recurrent genomic copy number aberrations. Specific loss at 8p23.2 was associated with advanced stage disease, and gain at 11q13.1 was found to be predictive of postoperative recurrence independent of stage and grade. Moreover, comparison with an independent set of metastases revealed approximately 40 candidate markers associated with metastatic potential. Copy number aberrations at these loci may define metastatic genotypes.

* To whom correspondence should be addressed at: PO Box 808, University of California at San Francisco, San Francisco, CA 94143, USA. Tel: +1 4155027067; Fax: +1 4155025665; Email: collins{at}cc.ucsf.edu


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