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

Publikation

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

Wissenschaftlicher Artikel/Review - 03.05.2022

Rodriguez-Calero Antonio, Gallon John, Akhoundova Dilara, Maletti Sina, Ferguson Alison, Cyrta Joanna, Amstutz Ursula, Garofoli Andrea, Paradiso Viola, Tomlins Scott A, Hewer Ekkehard, Genitsch Vera, Fleischmann Achim, Vassella Erik, Rushing Elisabeth J, Grobholz Rainer, Fischer Ingeborg, Jochum Wolfram, Cathomas Gieri, Osunkoya Adeboye O, Bubendorf Lukas, Moch Holger, Thalmann George, Ng Charlotte K Y, Gillessen Silke, Piscuoglio Salvatore, Rubin Mark A

Zitation

Rodriguez-Calero A, Gallon J, Akhoundova D, Maletti S, Ferguson A, Cyrta J, Amstutz U, Garofoli A, Paradiso V, Tomlins S, Hewer E, Genitsch V, Fleischmann A, Vassella E, Rushing E, Grobholz R, Fischer I, Jochum W, Cathomas G, Osunkoya A, Bubendorf L, Moch H, Thalmann G, Ng C, Gillessen S, Piscuoglio S, Rubin M. Alterations in homologous recombination repair genes in prostate cancer brain metastases. Nat Commun 2022; 13:2400.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

Nat Commun 2022; 13

Veröffentlichungsdatum

03.05.2022

eISSN (Online)

2041-1723

Seiten

2400

Kurzbeschreibung/Zielsetzung

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.