Homologous recombination repair status in metastatic prostate cancer by next-generation sequencing and functional immunofluorescence
Metastatic prostate cancer (mPC) is enriched for homologous recombination repair (HRR) gene alterations, which have prognostic and predictive value. Routine clinical implementation of next-generation sequencing (NGS) is still limited. We investigated the association between genomic and functional loss of HRR, using NGS and RAD51 immunofluorescence (RAD51-IF) in 219 primary or metastatic biopsies from 187 patients with stage IV prostate cancer. NGS showed frequent genomic alterations in TP53 (40%), AR (15%), PTEN (14%), FOXA1 (12%), MYC (10%), BRCA2 (9%), ATM (8%), and BRCA1 (2%). We pursued RAD51-IF in 206 samples; of those, 139/206 (67%) were evaluable. 21% of samples had RAD51-low score compatible with HRR deficiency (HRD). RAD51-IF showed high sensitivity (71%) and specificity (86%) for BRCA1/2 alterations. Patients with RAD51-low scores experienced longer progression-free survival (PFS) on poly(ADP-ribose) polymerase inhibitors (PARPi) or platinum chemotherapy. RAD51-IF is feasible in routine clinical samples from patients with mPC and is associated with clinically relevant HRR gene alterations.
Authors
- Joan Carles (ORCID: https://orcid.org/0000-0002-9983-5934)
- M. Cuadras (ORCID: https://orcid.org/0000-0003-4715-9230)
- Gisela Mir Arnau (ORCID: https://orcid.org/0000-0002-9005-3485)
- Matías de Albert (ORCID: https://orcid.org/0000-0002-6664-8104)
- Luisa Delgado-Serrano (ORCID: https://orcid.org/0000-0003-4845-1591)
- Xavier Maldonado (ORCID: https://orcid.org/0000-0003-2045-4723)
- Jacques Planas (ORCID: https://orcid.org/0000-0002-0222-584X)
- María Eugenia Semidey (ORCID: https://orcid.org/0000-0001-8539-9265)
- Joaquı́n Mateo (ORCID: https://orcid.org/0000-0001-5336-2548)
- Daniel Aguilar (ORCID: https://orcid.org/0000-0001-7520-4508)
- Mariona Figols (ORCID: https://orcid.org/0000-0001-7563-3812)
- Lara Nonell (ORCID: https://orcid.org/0000-0002-8538-8213)
- Sara Simonetti (ORCID: https://orcid.org/0000-0003-2406-030X)
- Alba Mas
- Sarai Córdoba-Terreros
- Irene Casanova‐Salas (ORCID: https://orcid.org/0000-0002-0499-1038)
- Alba Llop‐Guevara (ORCID: https://orcid.org/0000-0002-7913-9472)
- Sara Cros (ORCID: https://orcid.org/0000-0001-8279-784X)
- Rafael Morales‐Barrera (ORCID: https://orcid.org/0000-0001-7398-0685)
- Ana P. Vivancos (ORCID: https://orcid.org/0000-0003-2888-6512)
- Violeta Serra (ORCID: https://orcid.org/0000-0001-6620-1065)
- David Marmolejo
- Richard Mast (ORCID: https://orcid.org/0000-0001-6005-800X)
- Cristina Suárez (ORCID: https://orcid.org/0000-0002-0502-5528)
- Paolo Giovanni Nuciforo (ORCID: https://orcid.org/0000-0003-1380-0990)
- Sara Arce‐Gallego (ORCID: https://orcid.org/0009-0009-7294-0011)
- Rodrigo Dienstmann (ORCID: https://orcid.org/0000-0001-5997-318X)
- Pablo Cresta Morgado (ORCID: https://orcid.org/0000-0002-7502-8599)
- Paula Romero-Lozano
- Macarena González
Institutions
- Universitat de Vic - Universitat Central de Catalunya (ES)
- Hebron University (PS)
- Althaia (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Hospital General de Granollers (ES)
- Vall d'Hebron Hospital Universitari (ES)
- Vall d'Hebron Institute of Oncology (ES)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.101937
- Citations
- 7
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 7.32
Funders
- U.S. Department of Defense
- Prostate Cancer Foundation
- AstraZeneca
- Fundación Cellex
- Centres de Recerca de Catalunya
- Generalitat de Catalunya
- European Society for Medical Oncology
- CRIS Cancer Foundation
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación
- Congressionally Directed Medical Research Programs