Testing Mutual Exclusivity of ETS Rearranged Prostate Cancer
MA Svensson, CJ LaFargue, D Pflueger, N Kitabayashi, AK Tewari, F Demichelis, MA Rubin. Weill Cornell Medical College, New York, NY; University Hospital of Orebro, Orebro, Sweden
Background: Prostate cancer is a clinically heterogeneous and multifocal disease. More than 80% of patients with prostate cancer harbor multiple geographically discrete cancer foci at the time of diagnosis. Emerging data suggest that these foci are molecularly distinct consistent with the hypothesis that they arise as independent clones. One of the strongest arguments is the heterogeneity observed in the status of ETS rearrangements between discrete tumor foci. The clonal evolution of individual prostate cancer foci based on recent studies demonstrates intra-tumoral homogeneity but inter-tumoral heterogeneity. The issue of multifocality and interfocal heterogeneity is important and has not been fully elucidated due to lack of the systematic evaluation of ETS rearrangements in multiple tumor sites.
Design: The current study investigates the frequency of multiple ETS gene rearrangements within the same focus and between different cancer foci. Fluorescence in-situ hybridization (FISH) assays were designed to detect the four most common recurrent ETS gene rearrangements in a cohort of 88 men with localized prostate cancer.
Results: We found ERG, ETV1, and ETV5 rearrangements in 51% (44/86), 6% (5/85), and 1% (1/86), respectively. None of the cases demonstrated ETV4 rearrangements. Mutual exclusiveness of ETS rearrangements was observed in the vast majority of cases, however in six cases we discovered multiple ETS or 5 prime fusion partner rearrangements within the same tumor focus.
Conclusions: Our results demonstrate an additional level of complexity concerning the distribution of gene rearrangements in prostate cancer. This is exemplified by our observation that multiple rearrangements can exist within the prostate and can also occur within the same tumor focus. In conclusion, we provide further evidence for prostate cancer tumor heterogeneity with the identification of multiple concurrent ETS rearrangements.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 135, Wednesday Afternoon