ID

45703

Descrizione

Principal Investigator: Scott M. Dehm, PhD, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, Departments of Laboratory Medicine and Pathology and Urology, University of Minnesota, Minneapolis, MN, USA MeSH: Prostatic Neoplasms https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001223 Molecularly-targeted therapies for advanced prostate cancer include castration modalities that suppress ligand-dependent transcriptional activity of the androgen receptor (AR). However, persistent AR signaling undermines therapeutic efficacy and promotes progression to lethal castration-resistant prostate cancer (CRPC), even when patients are treated with potent second-generation AR-targeted therapies abiraterone and enzalutamide. Here we define diverse AR genomic structural rearrangements (AR-GSRs) as a class of molecular alterations occurring in one third of CRPC-stage tumors. AR-GSRs occur in the context of copy-neutral and amplified AR and display heterogeneity in breakpoint location, rearrangement class, and sub-clonal enrichment in tumors within and between patients. Despite this heterogeneity, one common outcome in tumors with high sub-clonal enrichment of AR-GSRs is outlier expression of diverse AR variant species lacking the ligand binding domain and possessing ligand-independent transcriptional activity. Collectively, these findings reveal AR-GSRs as important drivers of persistent AR signaling in CRPC.

collegamento

dbGaP-study=phs001223

Keywords

versioni (1)

1. 16/05/23 16/05/23 - Chiara Middel

Titolare del copyright

Scott M. Dehm, PhD, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, Departments of Laboratory Medicine and Pathology and Urology, University of Minnesota, Minneapolis, MN, USA

Caricato su

16 maggio 2023

DOI

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