Defining and Functionally Characterizing the Epigenome in Lethal Prostate Cancer
Abstract
Prostate cancer (PCa) is dependent on the androgen receptor (AR) at all stages of the disease. The centrality of the clinical role of this hormone-driven transcription factor (TF) in PCa renders it an ideal tumor type in which to study epigenetics. Using chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) in human radical prostatectomy (RP) specimens, we charted the AR cistrome - the universe of all AR binding sites in the genome. We observed that the AR cistrome undergoes significant alterations during the transition from localized to metastatic disease that are strikingly consistent across patients. This finding underlies our hypothesis that aberrant epigenetic signaling helps drive prostate PCa progression and provides the foundation for a deeper interrogation into the PCa epigenome across disease states in vivo. As part of this project, we have begun to define the genome-wide landscape of active enhancers and open across PCa states. The contents of these maps, in turn, guide screens that will identify regulatory elements associated with treatment resistance and key proteins binding to clinically relevant enhancers. Characterizing changes in the epigenome and its associated transcriptional programs will identify new therapeutic targets as well as biomarkers for therapy response and patient prognostication.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1201587
Entities
People
- Matthew L Freedman
Organizations
- Dana–Farber Cancer Institute