The somatic clinico-genomics of localized, non-indolent prostate cancer

Abstract

Prostate cancer is the second most frequently diagnosed non-skin male malignancy worldwide, with over 1.1 million new diagnoses each year. Population screening based on serum prostate-specific antigen (PSA) has shifted the disease burden toward earlier stage, localized disease. However, clinical outcomes for localized prostate cancer are highly heterogeneous, despite the use of clinical prognostic factors (PSA, Gleason grade, and TNM stage). Recent advances in massively-parallel DNA sequencing and computational biology have permitted detailed genomic analyses of all major human cancer types, including prostate cancer. However, the long natural history of prostate cancer has largely precluded rapid translation of this knowledge into clinical practice. Herein, we provide a “state of the field” overview of prostate cancer genomics, with particular focus on localized, non-indolent disease. We discuss recurrent somatic aberrations, across multiple mutational classes, which characterize this disease state, and suggest strategies through which an improved understanding of these molecular aberrations may be utilized in the curative setting. Finally, we summarize the major outstanding questions in prostate cancer genomics, and discuss hypotheses and potential strategies to begin to address these questions.

Keywords

Prostate cancer / genomics / biomarkers / clinical outcome

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