Genomic Alteration Burden in Advanced Prostate Cancer and Therapeutic Implications

The increasing number of patients with sequenced prostate cancer genomes enables us to study not only individual oncogenic mutations, but also capture the global burden of genomic alterations. Here we review the extent of tumor genome mutations and chromosomal structural variants in various clinical states of prostate cancer, and the related prognostic information. Next, we discuss the underlying mutational processes that give rise to these various alterations, and their relationship to the various molecular subtypes of prostate cancer. Finally, we examine the relationships between the tumor mutation burden of castration-resistant prostate cancer, DNA repair defects, and response to immune checkpoint inhibitor therapy.