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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA069568-11
Application #
7468643
Study Section
Special Emphasis Panel (ZCA1-RPRB-M (J1))
Project Start
2008-06-01
Project End
2013-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
11
Fiscal Year
2008
Total Cost
$281,821
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Rye, Morten Beck; Bertilsson, Helena; Andersen, Maria K et al. (2018) Cholesterol synthesis pathway genes in prostate cancer are transcriptionally downregulated when tissue confounding is minimized. BMC Cancer 18:478
Xie, Yuanyuan; Cao, Zhen; Wong, Elissa Wp et al. (2018) COP1/DET1/ETS axis regulates ERK transcriptome and sensitivity to MAPK inhibitors. J Clin Invest 128:1442-1457
Singhal, Udit; Wang, Yugang; Henderson, James et al. (2018) Multigene Profiling of CTCs in mCRPC Identifies a Clinically Relevant Prognostic Signature. Mol Cancer Res 16:643-654
Wang, Xiaoju; Qiao, Yuanyuan; Asangani, Irfan A et al. (2017) Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer. Cancer Cell 31:532-548.e7
Blattner, Mirjam; Liu, Deli; Robinson, Brian D et al. (2017) SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling. Cancer Cell 31:436-451
Dai, Xiangpeng; Gan, Wenjian; Li, Xiaoning et al. (2017) Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4. Nat Med 23:1063-1071
Lin, Ke-Chih; Torga, Gonzalo; Wu, Amy et al. (2017) Epithelial and mesenchymal prostate cancer cell population dynamics on a complex drug landscape. Converg Sci Phys Oncol 3:
Chen, Weiqiang; Allen, Steven G; Reka, Ajaya Kumar et al. (2016) Nanoroughened adhesion-based capture of circulating tumor cells with heterogeneous expression and metastatic characteristics. BMC Cancer 16:614
Hu, Shuhuan; Liu, Guangyu; Chen, Weiqiang et al. (2016) Multiparametric Biomechanical and Biochemical Phenotypic Profiling of Single Cancer Cells Using an Elasticity Microcytometer. Small 12:2300-11
Piert, Morand; Montgomery, Jeffrey; Kunju, Lakshmi Priya et al. (2016) 18F-Choline PET/MRI: The Additional Value of PET for MRI-Guided Transrectal Prostate Biopsies. J Nucl Med 57:1065-70

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