The Role of Genomic Diversity in Clinically High-Risk Prostate Cancer
Abstract
We hypothesize that the genomic diversity of localized prostate cancer predicts for metastatic spread of high-risk disease and is driven by specific oncogenes and tumor suppressors. Specific Aims. We will first determine if genomic diversity predicts metastasis and lethality of high-risk prostate cancer (Specific Aim #1). We will then use a cohort of at least 750 prostate cancers with DNA whole-genome sequencing to identify specific driver genes that influence prostate cancer genomic diversity (Specific Aim #2).Study Design: Aim #1. We have accrued 153 NCCN high-risk localized prostate cancers with high-coverage tumor and normal whole-genome sequencing. PGA and subclone number are the two measures of genomic diversity that most tightly predict metastasis of intermediate-risk prostate cancer. To rigorously test that association in high-risk disease we will perform high-coverage whole genome sequencing of tumor and blood normal samples from 100 NCCN high-risk localized prostate cancers with long-term outcome data. We will then determine whether these metrics individually and together predict metastasis and prostate cancer specific mortality.Study Design: Aim #2. We have accumulated 750 localized prostate cancers with high-coverage tumor and normal whole-genome sequencing across all risk groups. BothPGA and subclone number vary widely within this cohort. To determine if specific driver somatic mutations influence these metrics of genomic diversity, we will use statistical modeling. We will quantify how each recurrent driver mutation influences the genomic diversity of a cancer, controlling for clinico-epidemiologic features like age and grade.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2023
- Accession Number
- AD1212036
Entities
People
- Paul C. Boutros
Organizations
- University of California, Los Angeles