Homologous Recombination Deficiency and Genomic Alterations in Advanced Prostate Cancer: Insights for Precision Therapy - PubMed
4 hours ago
- #Homologous recombination
- #BRCA
- #Precision medicine
- HRDsig is emerging as a predictor of PARP-inhibitor response in advanced prostate cancer.
- Comprehensive genomic profiling was performed on 22,061 cases, with 10.2% being HRDsig+.
- HRDsig+ cases were enriched for BRCA2, RB1, MYC, RAD21, and AR alterations.
- BRCA2-loss and BRCA2-svmut cases showed higher genomic alteration burden and enrichment for RB1 alterations.
- BRCA2-loss cases displayed lower TMB-high incidence, while BRCA2-svmut showed higher MSI-high and TMB-high incidence.
- Most BRCA2 alterations were bi-allelic, with rare concurrent alterations in other HRR genes.
- BRCA2-loss cases showed robust HRD features, suggesting higher sensitivity to PARPi.
- Findings highlight the relevance of HRDsig and CGP in refining patient selection for PARPi therapy.