The Influence of Germline Variation on Prostate Cancer RNA Circularization

Principal Investigators: Paul Boutros, PhD, MBA (University of California, Los Angeles), Robert Reiter MD (University of California, Los Angeles), Huihui Ye, MD (University of California, Los Angeles)

Description: 

• Prostate cancer is one of the most heritable forms of cancer, and a number of heritable (“germline”) genomic alterations that increase risk for prostate cancer have been identified. For instance, patients with specific versions of DNA Damage Repair (DDR) genes such as BRCA2, have a much higher likelihood of diagnosis and of dying of their disease.  However, how germline genome features influence the prostate cancer initiation and progression remain unclear.
• Circular RNA are a recently discovered class of RNA that form covalent circular structures and have many different cellular functions, in normal processes as well as in diseases such as cancer. The role of circular RNA in prostate cancer remains largely unexplored.
• Boutros and team hypothesize that germline genomic features impact the circular RNA landscape and have a role in localized prostate cancer.
• In this project, the team will determine whether common (>5% population frequency) germline features influence the circular RNA landscape of localized prostate cancer, using samples from a biobank of prostate cancer patient tissues.
• Whether rare (<5% population frequency) deleterious germline alterations in DDR genes influence the circular RNA landscape of localized prostate cancer will be investigated.
• In addition, the team will determine how the circular RNA landscape of localized prostate cancer differs between patients of different ancestries.
• If successful, this project will uncover the ways in which a patient’s germline genome influences prostate cancer evolution via regulation of the unexplored landscape of circular RNAs. These studies will improve our understanding of how to prevent, diagnose, prognose and treat lethal prostate cancer.

What this means to patients:  Dr. Boutros and team will perform the first study of the way in which the germline genome influences the circular RNA landscape of prostate cancer.  These studies will greatly improve understanding of prostate cancer biology including in patients of different ancestries and lay the groundwork for the development of new risk prediction tools, prognostic biomarkers, and treatment opportunities.