The prostate cancer genome: perspectives and potential.

Overview

OBJECTIVES: Prostate cancer has a variable clinical course, and molecular characterization has revealed striking mutational heterogeneity that may underlie the unpredictable clinical behavior of the disease. Advances in technology have resulted in a rapid expansion of our understanding of the genomic events responsible for the development and progression of prostate cancer. In this review, we discuss the genomic alterations underlying prostate cancer, and potential to utilize this knowledge for diagnostic and prognostic benefit. METHODS AND MATERIALS: We reviewed the relevant literature, with a focus on recent studies on somatic alterations in prostate cancer. RESULTS: Pathways known to affect tumorigenesis across a wide spectrum of tissues are dysregulated, such as the PI3K pathway, cell cycle control, and chromatin regulation. Lesions more specific to prostate cancer include alterations in androgen signaling, gene fusions of ETS transcription factors, and mutations in SPOP. Accumulating data suggests that prostate cancer can be subdivided based on a molecular profile of these genetic alterations. CONCLUSIONS: These findings raise the possibility that prostate cancer could transition from a poorly understood, heterogeneous disease with a variable clinical course to a collection of homogenous subtypes, identifiable by molecular criteria, associated with distinct risk profiles, and perhaps amenable to specific management strategies or targeted therapies.