Genomic Alteration Burden in Advanced Prostate Cancer and Therapeutic Implications

Matthew J Ryan; Rohit Bose

doi:10.3389/fonc.2019.01287

Genomic Alteration Burden in Advanced Prostate Cancer and Therapeutic Implications

Front Oncol. 2019 Nov 22:9:1287. doi: 10.3389/fonc.2019.01287. eCollection 2019.

Authors

Matthew J Ryan^{1

2

3}, Rohit Bose^{2

3

4

5

6}

Affiliations

¹ Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA, United States.
² Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, United States.
³ Department of Anatomy, University of California, San Francisco, San Francisco, CA, United States.
⁴ Departments of Medicine and Urology, University of California, San Francisco, San Francisco, CA, United States.
⁵ UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, United States.
⁶ UCSF Benioff Initiative for Prostate Cancer Research, San Francisco, CA, United States.

Abstract

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.

Keywords: aneuploidy; copy number alteration; immune checkpoint inhibitor; mismatch repair deficiency; prostate cancer; structural variants; tumor mutation burden.

Publication types

Review

Grants and funding

K08 CA226348/CA/NCI NIH HHS/United States