ID
45703
Beschreibung
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.
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Stichworte
Versionen (1)
- 16.05.23 16.05.23 - Chiara Middel
Rechteinhaber
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
Hochgeladen am
16. Mai 2023
DOI
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Lizenz
Creative Commons BY 4.0
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dbGaP phs001223 Analysis of AR Gene Rearrangements in Prostate Cancer
Subject ID, gender, prostate cancer onset age, presence of metastases, primary tumor, metastasis, or transformed cell line, and Gleason score of participants with prostate cancer and involved in the "Analysis of AR Gene Rearrangements in Prostate Cancer" project.
- StudyEvent: SEV1
- Eligibility Criteria
- Subject ID, consent group, and affection status of participants with prostate cancer and involved in the "Analysis of AR Gene Rearrangements in Prostate Cancer" project.
- Subject ID, sample ID, and sample use variable obtained from participants with prostate cancer and involved in the "Analysis of AR Gene Rearrangements in Prostate Cancer" project.
- Subject ID, gender, prostate cancer onset age, presence of metastases, primary tumor, metastasis, or transformed cell line, and Gleason score of participants with prostate cancer and involved in the "Analysis of AR Gene Rearrangements in Prostate Cancer" project.
- Sample ID, analyte type, body site where sample was obtained, histological type, and tumor status of samples obtained from participants with prostate cancer and involved in the "Analysis of AR Gene Rearrangements in Prostate Cancer" project.
Ähnliche Modelle
Subject ID, gender, prostate cancer onset age, presence of metastases, primary tumor, metastasis, or transformed cell line, and Gleason score of participants with prostate cancer and involved in the "Analysis of AR Gene Rearrangements in Prostate Cancer" project.
- StudyEvent: SEV1
- Eligibility Criteria
- Subject ID, consent group, and affection status of participants with prostate cancer and involved in the "Analysis of AR Gene Rearrangements in Prostate Cancer" project.
- Subject ID, sample ID, and sample use variable obtained from participants with prostate cancer and involved in the "Analysis of AR Gene Rearrangements in Prostate Cancer" project.
- Subject ID, gender, prostate cancer onset age, presence of metastases, primary tumor, metastasis, or transformed cell line, and Gleason score of participants with prostate cancer and involved in the "Analysis of AR Gene Rearrangements in Prostate Cancer" project.
- Sample ID, analyte type, body site where sample was obtained, histological type, and tumor status of samples obtained from participants with prostate cancer and involved in the "Analysis of AR Gene Rearrangements in Prostate Cancer" project.
C2348585 (UMLS CUI [1,2])