The mutational landscape of prostate cancer

Christopher E. Barbieri, Chris H. Bangma, Anders Bjartell, James W.F. Catto, Zoran Culig, Henrik Grönberg, Jun Luo, Tapio Visakorpi, Mark A. Rubin

Research output: Contribution to journalReview article

Abstract

Context 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. Objective 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. Evidence acquisition We reviewed the relevant literature, with a particular focus on recent studies on somatic alterations in PCa. Evidence synthesis 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. Conclusions 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.

Original languageEnglish (US)
Pages (from-to)567-576
Number of pages10
JournalEuropean Urology
Volume64
Issue number4
DOIs
StatePublished - Oct 1 2013

Keywords

  • Copy number aberrations
  • Genomics
  • Oncogene
  • Sequencing
  • Tumor suppressor

ASJC Scopus subject areas

  • Urology

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    Barbieri, C. E., Bangma, C. H., Bjartell, A., Catto, J. W. F., Culig, Z., Grönberg, H., Luo, J., Visakorpi, T., & Rubin, M. A. (2013). The mutational landscape of prostate cancer. European Urology, 64(4), 567-576. https://doi.org/10.1016/j.eururo.2013.05.029