Integrated Meta-Analysis of Prostate Cancer Genomes
Abstract
Prostate Cancer: Prostate cancer is the most common non-skin cancer in men in the United States. It afflicts over 10% of men during the course of their lives. While many prostate cancers are nonlethal, others are extremely aggressive and kill men rapidly. Even the nonlethal cancers can have large effects on a man’s quality of life and large financial costs. To try to reduce prostate cancer death and maximize patient length and quality of life, clinicians and patients make a large number of decisions together. These include whether any treatment is necessary; whether surgery or radiotherapy is helpful; what frequency of monitoring is most appropriate; when and how drugs should be deployed; how to handle castrate-resistant disease; and many others. At its heart, the management of prostate cancer is all about these joint decisions that men make, supported by their caregivers and clinicians. Today, almost all of these life-changing decisions are made without using any information from the prostate cancer genome. Prostate Cancer Genomics: Cancer is at its root a disease of the genome. Some of the three billion letters of DNA present in each cell will mutate, with one letter replacing another or some being deleted or copied. These mutations can lead some cells to grow faster or to be less capable of repairing new mutations. As a result, cancers slowly emerge over time, becoming more and more aggressive. However, while DNA mutations underlie the growth of prostate cancer, this information has not generally been helpful in improving care for prostate cancer patients. In most other cancer types, DNA sequencing has transformed care, creating opportunities for new targeted drugs and highly accurate biomarkers to support clinical decision-making. DNA sequencing of prostate cancer has had much less impact on patient care. There are a few important exceptions, like the widespread testing for BRCA2 germline mutations in men with aggressive or metastatic disease. Nevertheless, overall DNA sequencing of prostate cancers has not had the transformative impact it has for other cancer types. Objective: One key reason genomic information has been less useful in prostate cancer is that the very large datasets generated are difficult for researchers to use effectively. Many research groups in several countries have sequenced DNA from prostate tumors donated by patients. However, each group has focused on a different aspect of the disease. This makes sense: focus helps to make individual studies successful! However, this same focus means that the full picture of prostate cancer evolution is unclear because data are not centralized. DNA sequencing data exists in multiple different databases, analyzed with different algorithms, and is difficult to use efficiently. Our objective is to centralize all prostate cancer DNA sequencing data, analyze it with cutting-edge methods, and make that available to prostate cancer researchers around the world. What do we hope to find? Beyond creating a resource, we will use the reanalyzed prostate DNA sequencing data to answer two key questions. First, how do prostate cancers evolve? We will identify which mutations happen early (and thus are good drug targets) and which ones happen later, just before metastasis or resistance to therapy (and thus might be good biomarkers). Second, what is the full list of all genes that are mutated repeatedly in prostate cancer? This list will give us a set of candidate drug targets and will allow future studies to focus on only those regions of the genome mutated in prostate cancer. This will accelerate research by reducing wasted time and money expended in studying genomic areas not mutated in this cancer type. Applicability: This proposal has the potential to help all prostate cancer patients by bringing the community together to use existing data more cleverly and intensely. Each existing DNA sequencing dataset has required the investment
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210247
Entities
People
- Paul C. Boutros
Organizations
- United States Army
- University of California, Los Angeles