Clonal origin and spread of metastatic prostate cancer

    1. Scott M Dehm1,2,3
    1. 1Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
    2. 2Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
    3. 3Department of Urology, University of Minnesota, Minneapolis, MN, USA
    1. Correspondence should be addressed to S M Dehm; Email: dehm{at}


    Metastatic disease is responsible for the majority of prostate cancer deaths. The standard treatment for metastatic disease is surgical or chemical castration in the form of androgen deprivation therapy. Despite initial success and disease regression, resistance to therapy ultimately develops and the disease transitions to castration-resistant prostate cancer, which is uniformly fatal. Thus, developing an understanding of genetic evolution in metastasis and in response to therapy has been a focus of recent studies. Large-scale sequencing studies have provided an expansive catalog of the mutation events that occur in the prostate cancer genome at various stages of disease progression. Small-scale studies have interrogated the genomic composition of multiple metastatic sites within individual patients or have tracked clonal evolution longitudinally in tissues, circulating tumor cells, or circulating tumor DNA. Collectively, these efforts have provided a new conceptual framework for understanding the origin of prostate cancer, as well as the origin and evolution of metastatic disease. In this review, we highlight these recent insights into the spatiotemporal landscape of genetic evolution of prostate cancer.

    • Received 4 March 2016
    • Accepted 17 March 2016
    • Made available online as an Accepted Preprint 1 April 2016
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