Employing a bioinformatics approach to analyze prostate cancer gene expression profiles, we identified recurrent gene fusions/translocations in the majority of prostate cancers (Tomlins et al, Science 2005). Specifically, we identified the androgen regulatory elements of TMPRSS2 fused to the members of the ETS family of transcription factors including ERG, ETV1, ETV4 and ETV5. Analogous to hematological malignancies, gene fusions/translocations identified in prostate cancer may represent pathognomonic biomarkers and molecular sub-types of disease. In this application, we plan to focus our efforts on characterizing this new class of gene fusion biomarkers. Preliminary work done by our group and others suggest that molecular subtypes as well as transcript variants of gene fusions may be associated with clinical sub-types of prostate cancer. The central hypothesis of this application is that molecular sub-types based on gene fusions and variants will be useful predictors of the aggressive potential of clinically localized prostate cancer and thus guide treatment. Given this, 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 outcome and/or aggressiveness of disease in a radical prostatectomy cohort.
Specific Aim 3. Characterize associations of molecular sub-types of prostate cancer with clinical outcome and/or aggressiveness of disease using prostate needle biopsy samples.

Public Health Relevance

Project Narrative: The discovery of genes fused together is a major advancement in the understanding of prostate cancer. This proposal is about using these """"""""gene fusions"""""""" to identify prognostic categories to improve approaches to the treatment of prostate cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA132874-04
Application #
8204900
Study Section
Cancer Genetics Study Section (CG)
Program Officer
Martin, Damali
Project Start
2009-03-01
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
4
Fiscal Year
2012
Total Cost
$248,776
Indirect Cost
$87,756
Name
University of Michigan Ann Arbor
Department
Pathology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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