Androgen regulation of prostate cancer gene fusions

Abstract

Recurrent chromosomal rearrangements were not well characterized in epithelial malignancies until the recent discovery of recurrent fusions of TMPRSS2 and ETS transcription factors in prostate cancer. Since the initial discovery of the TMPRSS2:ETS gene fusions, multiple other 5′ and 3′ fusion partners have been discovered, which led to the identification of five different classes of ETS gene rearrangements to date. These rearrangements demonstrate variable response to androgen stimulation, and ultimately, may help tailor androgen-deprivation therapy for patients with advanced prostate cancer. Initial studies have demonstrated that ETV1 overexpression mediates invasion in prostate cell lines, though secondary factors may be required for the development of frank malignancy. TMPRSS2:ETS gene fusions may confer a more aggressive phenotype, and fusion status has been linked to adverse clinical factors, such as higher tumor stage and nodal metastases. ETS factor fusions are likely an important contributor to human prostate cancer development and progression, though more research will be needed to elucidate their regulation by androgen and clinical functionality. Ultimately, identification of distinct gene fusion status may allow for risk stratification and tailored treatment of patients with prostate cancer. © 2009 Springer-Verlag New York.