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Alterations in homologous recombination repair genes in prostate cancer brain metastases.
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.
Afiliação
  • Rodriguez-Calero A; Department for BioMedical Research, University of Bern, Bern, Switzerland.
  • Gallon J; Institute of Pathology, University of Bern, Bern, Switzerland.
  • Akhoundova D; Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Maletti S; Department for BioMedical Research, University of Bern, Bern, Switzerland.
  • Ferguson A; Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland.
  • Cyrta J; Department for BioMedical Research, University of Bern, Bern, Switzerland.
  • Amstutz U; Department for BioMedical Research, University of Bern, Bern, Switzerland.
  • Garofoli A; Department of Oncology, Ludwig Cancer Centre, University of Lausanne, Lausanne, Switzerland.
  • Paradiso V; Department of Pathology, Institut Curie, University Paris Sciences et Lettres, Paris, France.
  • Tomlins SA; Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Hewer E; Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Genitsch V; Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Fleischmann A; Departments of Pathology and Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Vassella E; Institute of Pathology, University of Bern, Bern, Switzerland.
  • Rushing EJ; Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Grobholz R; Institute of Pathology, University of Bern, Bern, Switzerland.
  • Fischer I; Institute of Pathology, University of Bern, Bern, Switzerland.
  • Jochum W; Institute of Pathology, Cantonal Hospital Thurgau, Münsterlingen, Switzerland.
  • Cathomas G; Institute of Pathology, University of Bern, Bern, Switzerland.
  • Osunkoya AO; Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
  • Bubendorf L; Institute of Pathology, Cantonal Hospital Aarau, Aarau, Switzerland.
  • Moch H; Institute of Pathology, Cantonal Hospital Aarau, Aarau, Switzerland.
  • Thalmann G; Institute of Pathology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
  • Ng CKY; Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
  • Gillessen S; Departments of Pathology and Laboratory Medicine, and Urology, Emory University School of Medicine, Atlanta, USA.
  • Piscuoglio S; Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Rubin MA; Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
Nat Commun ; 13(1): 2400, 2022 05 03.
Article em En | MEDLINE | ID: mdl-35504881
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Neoplasias Encefálicas Limite: Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Suíça
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Neoplasias Encefálicas Limite: Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Suíça