Guarding the Prostate Epigenome
Prostate cancer is more aggressive in African American men. Recent studies indicate for a role for epigenetics, the biology of how genes are turned on and off, in prostate carcinogenesis. This project will examine the role of an epigenetic modifier as a means to develop new therapies and biomarkers that can be utilized for patients affected by this malignancy.
The underlying basis for the aggressive nature of prostate cancer in African American men is unknown at this time. Multiple studies point to a role for epigenetics as playing a role in the pathogenesis of prostate cancer in tandem with investigations demonstrated differential epigenetic alterations in prostate cancer from African American men as compared with Caucasian men. Although alterations in the epigenome have long been implicated in prostate cancer, the mechanisms driving these changes and their biologic contribution remain poorly understood. Recent studies indicate a role for the epigenetic modifier TET2 in the pathogenesis of prostate cancer. TET2 is a bona fide tumor suppressor in leukemia.
- Assess the role of TET2 in two seminal events of the clinical course of prostate cancer: metastasis and the development of hormone refractory disease. In turn, we will utilize next generation sequencing to assess where TET2 mediates its effects in the prostate genome and the corresponding effects on the transcriptome.
- Assess the potential of the TET2/5-hmC axis as a predictive biomarker of aggressive disease in African American men with newly diagnosed prostate cancer.
- Conduct focus groups to determine attitudes toward biomarker utilization to facilitate decision making in African American men with newly diagnosed prostate cancer. The overall goal of the project is to provide new insight into the epigenetic landscape of prostate cancer as a means to identify novel targets and biomarkers for African American men diagnosed with this malignancy.