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A transcriptomic model for homologous recombination deficiency in prostate cancer
- Source :
- Prostate Cancer and Prostatic Diseases; December 2022, Vol. 25 Issue: 4 p659-665, 7p
- Publication Year :
- 2022
-
Abstract
- Background: Tumors with mutations associated with homologous recombination deficiency (HRD) are uncommon in prostate cancer (PCa) and variably responsive to PARP inhibition. To better identify tumors with HRD, we developed a transcriptomic signature for HRD in PCa (HRD-P). Methods: By using an established mutational signature, we created and validated HRD-P in six independent PCa cohorts (primary PCa, n= 8224; metastatic castration-resistant PCa [mCRPC], n= 328). Molecular and clinical features were compared between HRD-P+ tumors and those with single HR-gene mutations. Results: HRD-P+ tumors were more common than tumors with single HR-gene mutations in primary (201/491, 41% vs 32/491 6.5%) and mCRPC (126/328, 38% vs 82/328, 25%) cases, and HRD-P+ was more predictive of genomic instability suggestive of HRD. HRD-P+ was associated with a shorter time to recurrence following surgery and shorter overall survival in men with mCRPC. In a prospective trial of mCRPC treated with olaparib (n= 10), all three men with HRD-P+ experienced prolonged (>330 days) PSA progression-free survival. Conclusion: These results suggest transcriptomics can identify more patients that harbor phenotypic HRD than single HR-gene mutations and support further exploration of transcriptionally defined HRD tumors perhaps in conjunction with genomic markers for therapeutic application.
Details
- Language :
- English
- ISSN :
- 13657852 and 14765608
- Volume :
- 25
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Prostate Cancer and Prostatic Diseases
- Publication Type :
- Periodical
- Accession number :
- ejs57004575
- Full Text :
- https://doi.org/10.1038/s41391-021-00416-2