Cell reports. Medicine · 2025
Homologous recombination repair status in metastatic prostate cancer by next-generation sequencing and functional immunofluorescence.
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Arce-Gallego Sara, Cresta Morgado Pablo, Delgado-Serrano Luisa, Simonetti Sara, Gonzalez Macarena, Romero-Lozano Paula, Marmolejo David, Morales-Barrera Rafael, Arnau Gisela Mir, Semidey Maria Eugenia, Aguilar Daniel, Cordoba-Terreros Sarai, Mast Richard, de Albert Matias, Planas Jacques, Cuadras Mercè, Maldonado Xavier, Suarez Cristina, Casanova-Salas Irene, Figols Mariona, Cros Sara, Mas Alba, Nonell Lara, Dienstmann Rodrigo, Nuciforo Paolo, Vivancos Ana, Llop-Guevara Alba, Carles Joan, Serra Violeta, Mateo Joaquin
Аннотация
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.