Alterations in homologous recombination repair genes in prostate cancer brain metastases

Antonio Rodriguez-Calero, John Gallon, Dilara Akhoundova, Sina Maletti, Alison Ferguson, Joanna Cyrta, Ursula Amstutz, Andrea Garofoli, Viola Paradiso, Scott A. Tomlins, Ekkehard Hewer, Vera Genitsch, Achim Fleischmann, Erik Vassella, Elisabeth J. Rushing, Rainer Grobholz, Ingeborg Fischer, Wolfram Jochum, Gieri Cathomas, Adeboye O. Osunkoya, Lukas Bubendorf, Holger Moch, George Thalmann, Charlotte K. Y. Ng, Silke Gillessen, Salvatore Piscuoglio () and Mark A. Rubin ()
Additional contact information
Antonio Rodriguez-Calero: University of Bern
John Gallon: University of Basel
Dilara Akhoundova: University of Bern
Sina Maletti: University of Bern
Alison Ferguson: University of Bern
Joanna Cyrta: University Paris Sciences et Lettres
Ursula Amstutz: Bern University Hospital, University of Bern
Andrea Garofoli: University Hospital Basel, University of Basel
Viola Paradiso: University Hospital Basel, University of Basel
Scott A. Tomlins: University of Michigan Medical School
Ekkehard Hewer: University of Bern
Vera Genitsch: University of Bern
Achim Fleischmann: University of Bern
Erik Vassella: University of Bern
Elisabeth J. Rushing: University Hospital Zurich
Rainer Grobholz: Cantonal Hospital Aarau
Ingeborg Fischer: Cantonal Hospital Aarau
Wolfram Jochum: Cantonal Hospital St. Gallen
Gieri Cathomas: Cantonal Hospital Baselland
Adeboye O. Osunkoya: Emory University School of Medicine
Lukas Bubendorf: University Hospital Basel, University of Basel
Holger Moch: University Hospital Zurich
George Thalmann: Bern University Hospital
Charlotte K. Y. Ng: University of Bern
Silke Gillessen: Faculty of Biomedical Sciences, USI
Salvatore Piscuoglio: University of Basel
Mark A. Rubin: University of Bern

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30003-5

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DOI: 10.1038/s41467-022-30003-5

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