Exploiting Real-World Clinical Genomic Data to Discover Biomarkers and Address Outcome Disparity for Prostate Cancer
Abstract
All prostate cancer tumor cells will have the hallmark of mutated or altered DNA. Some of these DNA alterations can now be detected in the clinic using techniques of sequencing DNA of tumor cells from a biopsy. Tumor DNA sequencing generates data that requires computer software to analyze. As more of these tests are developed and applied in the clinic, tumors are profiled routinely for many patients in standard of care. These tests have generated data that represent a real-world accumulation of tumors from patients with various ancestry and ethnic backgrounds. However, despite these approved tests being offered routinely, there is still an under-representation of tumors profiled for some populations, such as those with African ancestry. Thus, it has been challenging to comprehensively study why prostate cancer mortality varies substantially between racial and ancestral backgrounds. These clinical tests typically profile whether mutations exist in a certain panel of genes that are known to be associated with cancer. However, these panels usually represent less than 0.2% of the human genome, resulting in missing information that may be crucial to understanding how the tumor may respond to treatment. For example, inherited DNA differences or variants are rarely fully captured even though they are important for determining ancestral marks that may be linked to tumor risk and outcome; also missed by these panels are scars throughout the genome, which are patterns or footprints of disrupted biological processes in the cells. To address these questions, we will analyze an unprecedented number of over 20,000 tumor samples profiled by DNA sequencing in the real-world clinical setting. Our objective is to develop innovative computer algorithms to analyze ancestry markers and DNA alterations throughout the entire genome, beyond the panel of selected genes. We aim to use these results to unravel the relationship between the DNA alteration patterns and ancestry markers to learn how they contribute to disparities in survival and to discover new biomarkers that predict how prostate cancers respond to treatment. The new tools developed in this project can be readily adapted into current workflows for an immediate impact for patients. This project will also contribute to the on-going efforts to accelerate prospective studies of prostate cancer patients with diverse ancestral backgrounds and advance precision oncology for underserved populations. Therefore, this work will directly address the PCRP Overarching Challenges to define the biology of lethal prostate cancer to reduce death and to advance our understanding of health disparities in prostate cancer through innovative approaches to exploit real-world clinical data for biomarker discovery.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310445
Entities
People
- Jian Carrot-zhang
Organizations
- Sloan-Kettering Institute
- United States Army