Testing mutual exclusivity of ETS rearranged prostate cancer.

TitleTesting mutual exclusivity of ETS rearranged prostate cancer.
Publication TypeJournal Article
Year of Publication2011
AuthorsSvensson MA, Lafargue CJ, MacDonald TY, Pflueger D, Kitabayashi N, Santa-Cruz AM, Garsha KE, Sathyanarayana UG, Riley JP, Yun CS, Nagy D, Kosmeder JW, Pestano GA, Tewari AK, Demichelis F, Rubin MA
JournalLab Invest
Date Published2011 Mar
KeywordsAged, Cell Transformation, Neoplastic, Cohort Studies, DNA-Binding Proteins, Gene Fusion, Gene Rearrangement, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Molecular Imaging, Neoplasm Staging, Oncogene Proteins, Fusion, Prostatic Neoplasms, Quantum Dots, Tissue Array Analysis, Trans-Activators, Transcription Factors

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 E26 transformation specific (ETS) rearrangements between discrete tumor foci. The clonal evolution of individual prostate cancer foci based on recent studies demonstrates intertumoral heterogeneity with intratumoral homogeneity. 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. The current study investigates the frequency of multiple 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, 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 majority of cases; however, in six cases, we discovered multiple ETS or 5' fusion partner rearrangements within the same tumor focus. In conclusion, we provide further evidence for prostate cancer tumor heterogeneity with the identification of multiple concurrent gene rearrangements.

Alternate JournalLab. Invest.
PubMed ID20975660
PubMed Central IDPMC3130188
Grant ListCA116337 / CA / NCI NIH HHS / United States
CA125612 / CA / NCI NIH HHS / United States
R01 AG021404 / AG / NIA NIH HHS / United States
U01 CA111275 / CA / NCI NIH HHS / United States