Alterations in homologous recombination repair genes in prostate cancer brain metastases.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_067B8F2489FA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Alterations in homologous recombination repair genes in prostate cancer brain metastases.
Périodique
Nature communications
Auteur⸱e⸱s
Rodriguez-Calero A., Gallon J., Akhoundova D., Maletti S., Ferguson A., Cyrta J., Amstutz U., Garofoli A., Paradiso V., Tomlins S.A., Hewer E., Genitsch V., Fleischmann A., Vassella E., Rushing E.J., Grobholz R., Fischer I., Jochum W., Cathomas G., Osunkoya A.O., Bubendorf L., Moch H., Thalmann G., Ng CKY, Gillessen S., Piscuoglio S., Rubin M.A.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
03/05/2022
Peer-reviewed
Oui
Volume
13
Numéro
1
Pages
2400
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Improved survival rates for prostate cancer through more effective therapies have also led to an increase in the diagnosis of metastases to infrequent locations such as the brain. Here we investigate the repertoire of somatic genetic alterations present in brain metastases from 51 patients with prostate cancer brain metastases (PCBM). We highlight the clonal evolution occurring in PCBM and demonstrate an increased mutational burden, concomitant with an enrichment of the homologous recombination deficiency mutational signature in PCBM compared to non-brain metastases. Focusing on known pathogenic alterations within homologous recombination repair genes, we find 10 patients (19.6%) fulfilling the inclusion criteria used in the PROfound clinical trial, which assessed the efficacy of PARP inhibitors (PARPi) in homologous recombination deficient prostate cancer. Eight (15.7%) patients show biallelic loss of one of the 15 genes included in the trial, while 5 patients (9.8%) harbor pathogenic alterations in BRCA1/2 specifically. Uncovering these molecular features of PCBM may have therapeutic implications, suggesting the need of clinical trial enrollment of PCBM patients when evaluating potential benefit from PARPi.
Mots-clé
Brain Neoplasms/drug therapy, Brain Neoplasms/genetics, Humans, Male, Mutation, Poly(ADP-ribose) Polymerase Inhibitors/pharmacology, Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use, Prostatic Neoplasms/drug therapy, Prostatic Neoplasms/genetics, Recombinational DNA Repair/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
04/05/2022 11:34
Dernière modification de la notice
15/07/2022 6:08
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