The Mutational Landscape of Prostate Cancer

• Published in: European urology Vol. 64; no. 4; pp. 567 - 576
• Main Authors: Barbieri, Christopher E., Bangma, Chris H., Bjartell, Anders, Catto, James W.F., Culig, Zoran, Grönberg, Henrik, Luo, Jun, Visakorpi, Tapio, Rubin, Mark A.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.10.2013; Elsevier
• Subjects: Biological and medical sciences; Biomarkers, Tumor - genetics; Clinical Medicine; Copy number aberrations; DNA Mutational Analysis; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Genetic Testing - methods; Genomics; Genomics - methods; Gynecology. Andrology. Obstetrics; Humans; Klinisk medicin; Male; Male genital diseases; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Molecular Targeted Therapy; Mutation; Nephrology. Urinary tract diseases; Oncogene; Patient Selection; Phenotype; Precision Medicine; Predictive Value of Tests; Prognosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Risk Factors; Sequencing; Signal Transduction - genetics; Tumor suppressor; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urology; Copy number aberrations; Sequencing; Tumor suppressor; Genomics; Oncogene; Nephrology; Urinary system disease; Prostate disease; Nucleotide sequence; Copy number; Malignant tumor; Urology; Genetics; Mutation; Onc gene; Genome; Male genital diseases; Prostate cancer; Cancer; Tumor suppressor gene
• ISSN: 0302-2838; 1873-7560; 1421-993X; 1873-7560
• DOI: 10.1016/j.eururo.2013.05.029

Prostate cancer (PCa) is a clinically heterogeneous disease with marked variability in patient outcomes. Molecular characterization has revealed striking mutational heterogeneity that may underlie the variable clinical course of the disease. In this review, we discuss the common genomic alterations that form the molecular basis of PCa, their functional significance, and the potential to translate this knowledge into patient care. We reviewed the relevant literature, with a particular focus on recent studies on somatic alterations in PCa. Advances in sequencing technology have resulted in an explosion of data regarding the mutational events underlying the development and progression of PCa. Heterogeneity is the norm; few abnormalities in specific genes are highly recurrent, but alterations in certain signaling pathways do predominate. These alterations include those in pathways known to affect tumorigenesis in a wide spectrum of tissues, such as the phosphoinositide 3-kinase/phosphatase and tensin homolog/Akt pathway, cell cycle regulation, and chromatin regulation. Alterations more specific to PCa are also observed, particularly gene fusions of ETS transcription factors and alterations in androgen signaling. Mounting data suggest that PCa can be subdivided based on a molecular profile of genetic alterations. Major advances have been made in cataloging the genomic alterations in PCa and understanding the molecular mechanisms underlying the disease. These findings raise the possibility that PCa could soon transition from being a poorly understood, heterogeneous disease with a variable clinical course to being a collection of homogenous subtypes identifiable by molecular criteria, associated with distinct risk profiles, and perhaps amenable to specific management strategies or targeted therapies. Prostate cancer is a clinically heterogeneous disease with marked variability in patient outcomes. Molecular characterization has revealed striking mutational heterogeneity that may underlie the variable clinical course of the disease and that may provide improved risk stratification and novel therapeutic targets.