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2022 Todd Boehly – PCF Young Investigator Award

Associating Germline Variants with Prostate Tumour Evolution and Lethality

Roni Haas, PhD
University of California, Los Angeles (UCLA)

Mentor: Paul Boutros, PhD, MBA

Description:

  • Prostate cancer is one of the most heritable cancer types, with ~57% of the risk of developing prostate cancer defined by inherited genetic variants. These variants differ dramatically across populations and are associated with clinical and therapeutic outcomes in ways that are difficult to predict. Uncovering the precise contributions of inherited genetic variants to prostate cancer development is critical for advancing patient management.
  • Dr. Roni Haas is studying how genetic variants contribute to prostate cancer biology.
  • A novel bioinformatic framework will be developed to map genetic variants to hallmark biological functions in cancer development and progression. This framework will include methods to predict the genetic component of pathway activities and link them to prostate cancer aggressiveness.
  • In addition, the relationships between genetic variants and cancer DNA methylation will be investigated in advanced prostate cancer. DNA methylation is a type of epigenetic mechanism in which chemical marks on the DNA regulate gene expression. These chemical marks determine whether genes in a given region can be expressed or not by changing the ability of proteins to interact with the DNA, and controlling how condensed vs. open a DNA region is.
  • If successful, this study will result in novel prognostic biomarkers for early detection and prediction of patient outcomes, and potential new targets for therapy. These will advance personalized clinical management in patients with prostate cancer.

What this means to patients: Prostate cancer is highly heritable, yet it remains unclear how genetic variants contribute to prostate cancer development and progression. Dr. Haas and team will link genetic variants to their role in disease development and progression, including how they contribute to hallmark cancer biology pathways and impact the cancer epigenome.