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Human Molecular Genetics Advance Access published online on May 11, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh155
© 2004 by Oxford University Press
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Article

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

Pamela L. Paris 1, Armann Andaya 1, Jane Fridlyand 1, Ajay N. Jain 1, Vivian Weinberg 1, David Kowbel 1, John H. Brebner 1, Jeff Simko 2, J. E. Vivienne Watson 1, Stas Volik 1, Donna G. Albertson 1, Daniel Pinkel 1, Janneke C. Alers 3, Theodorus H. van der Kwast 3, Kees J. Vissers 3, Fritz H. Schroder 4, Mark F. Wildhagen 4, Phillip G. Febbo 5, Arul M. Chinnaiyan 6, Kenneth J. Pienta 6, Peter R. Carroll 7, Mark A. Rubin 8, Colin Collins 9*, Herman van Dekken 3

1 UCSF Comprehensive Cancer Center, San Francisco, CA 94115, USA
2 UCSF Comprehensive Cancer Center, San Francisco, CA 94115, USA; UCSF Department of Anatomic Pathology, San Francisco, CA 94115, USA
3 Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
4 Department of Urology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
5 Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
6 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
7 Department of Urology, UCSF Comprehensive Cancer Center, San Francisco, CA 94115, USA
8 Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
9 UCSF Comprehensive Cancer Center, San Francisco, CA 94115, USA; Colin Collins, Box 808, UCSF, San Francisco, CA 94143, USA

* To whom correspondence should be addressed. E-mail: collins{at}cc.ucsf.edu.


  Abstract

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 (PSA) screening has resulted in earlier disease detection yet roughly 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 is comprised of 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 ~40 candidate markers associated with metastatic potential. Copy number aberrations at these loci may define metastatic genotypes.


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