Employing a bioinformatics approach to analyze prostate cancer gene expression profiles, we identifiedrecurrent gene fusions/translocations in the majority of prostate cancers (Tomlins et al, Science 2005). Thisrepresents a landmark discovery emanating from this project and our larger SPORE grant. Specifically, weidentified the androgen regulatory elements of TMPRSS2 fused to the members of the ETS family oftranscription factors including ERG, ETV1, and ETV4. Analogous to hematological malignancies, genefusions/translocations identified in prostate cancer may represent pathognomonic biomarkers and molecularsub-types of disease. In this renewal application, we plan to focus our efforts on characterizing this newclass of gene fusion biomarkers.Preliminary work done by our group and others suggest that molecular subtypes as well as transcriptvariants of gene fusions may be associated with clinical sub-types of prostate cancer. The central hypothesisof this renewal application is that molecular sub-types based on gene fusions and variants will be usefulpredictors of the aggressive potential of clinically localized prostate cancer and thus guide treatment. Giventhis, we propose the following Aims:
Specific Aim 1 : Discovery and nomination of novel molecular sub-types of prostate cancer.
Specific Aim 2 : Characterize associations of molecular sub-types of prostate cancer with clinical outcomeand/or aggressiveness of disease in a radical prostatectomy cohort.
Specific Aim 3. Characterize associations of molecular sub-types of prostate cancer with clinical outcomeand/or aggressiveness of disease using prostate needle biopsy samples.The success of the translational mission of this project and the SPORE was exemplified this year by ourintegrated team of investigators working together and utilizing SPORE resources to win the 1st annual AACRTeam Science Award for the discovery of the importance of the TMPRSS:ETS family gene fusions inprostate cancer tumorigenesis. This Award was established by the American Association for CancerResearch (AACR) to acknowledge and catalyze the growing importance of interdisciplinary teams to theunderstanding of cancer and/or the translation of research discoveries into clinical cancer applications.
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