Alterations in homologous recombination repair genes in prostate cancer brain metastases
| العنوان: | Alterations in homologous recombination repair genes in prostate cancer brain metastases |
|---|---|
| المؤلفون: | 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, Mark A. Rubin |
| المساهمون: | University of Zurich, Piscuoglio, Salvatore, Rubin, Mark A |
| المصدر: | Nature communications, vol. 13, no. 1, pp. 2400 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; ... (2022). Alterations in homologous recombination repair genes in prostate cancer brain metastases. Nature Communications, 13(1), p. 2400. Springer Nature 10.1038/s41467-022-30003-5 <http://dx.doi.org/10.1038/s41467-022-30003-5Test> |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Male, Multidisciplinary, Brain Neoplasms, Prostatic Neoplasms, Recombinational DNA Repair, General Physics and Astronomy, Brain Neoplasms/drug therapy, Brain Neoplasms/genetics, Humans, 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, 610 Medicine & health, 1600 General Chemistry, General Chemistry, Poly(ADP-ribose) Polymerase Inhibitors, General Biochemistry, Genetics and Molecular Biology, 3100 General Physics and Astronomy, 1300 General Biochemistry, Genetics and Molecular Biology, 10049 Institute of Pathology and Molecular Pathology, 570 Life sciences, biology |
| الوصف: | 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. |
| وصف الملف: | Rodriguez_NatComm_2022.pdf - application/pdf; application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d339acb753118a030885e55b80a56cbbTest https://www.zora.uzh.ch/id/eprint/222097Test/ |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d339acb753118a030885e55b80a56cbb |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |