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Whole genome scanning identifies genotypes associated with recurrence and metastasis in prostate tumors
Authors:Paris Pamela L  Andaya Armann  Fridlyand Jane  Jain Ajay N  Weinberg Vivian  Kowbel David  Brebner John H  Simko Jeff  Watson J E Vivienne  Volik Stas  Albertson Donna G  Pinkel Daniel  Alers Janneke C  van der Kwast Theodorus H  Vissers Kees J  Schroder Fritz H  Wildhagen Mark F  Febbo Phillip G  Chinnaiyan Arul M  Pienta Kenneth J  Carroll Peter R  Rubin Mark A  Collins Colin  van Dekken Herman
Affiliation:Comprehensive Cancer Center, University of California at San Francisco, 94115, USA.
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 screening has resulted in earlier disease detection, yet approximately 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.
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