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

Brain Neoplasms / drug therapy Humans Male Mutation Poly(ADP-ribose) Polymerase Inhibitors / pharmacology Prostatic Neoplasms / drug therapy Recombinational DNA Repair / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
03 05 2022
Historique:
received: 06 05 2020
accepted: 12 04 2022
entrez: 3 5 2022
pubmed: 4 5 2022
medline: 6 5 2022
Statut: 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.

Identifiants

DOI: 10.1038/s41467-022-30003-5 PMID: 35504881 PMC: PMC9065149
pubmed: 35504881
doi: 10.1038/s41467-022-30003-5
pii: 10.1038/s41467-022-30003-5
pmc: PMC9065149
doi:

Substances chimiques

Poly(ADP-ribose) Polymerase Inhibitors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2400

Subventions

Organisme : NCI NIH HHS
ID : P50 CA211024
Pays : United States

Informations de copyright

© 2022. The Author(s).

Références

Cell. 2015 May 21;161(5):1215-1228
pubmed: 26000489
Am J Surg Pathol. 2014 Jun;38(6):756-67
pubmed: 24705311
Nat Commun. 2019 Jul 18;10(1):3190
pubmed: 31320627
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Cancer Res. 2012 Nov 1;72(21):5454-62
pubmed: 22933060
Neoplasia. 2015 Apr;17(4):385-99
pubmed: 25925381
Curr Oncol Rep. 2012 Feb;14(1):48-54
pubmed: 22012633
Cancer Cell. 2020 Sep 14;38(3):350-365.e7
pubmed: 32619406
Clin Cancer Res. 2017 Jun 1;23(11):2617-2629
pubmed: 28572256
Genome Med. 2018 Apr 25;10(1):33
pubmed: 29695279
Mol Cancer Ther. 2011 Sep;10(9):1644-55
pubmed: 21709130
J Mol Diagn. 2000 Feb;2(1):20-8
pubmed: 11272898
Clin Cancer Res. 2020 Jun 1;26(11):2673-2680
pubmed: 32071115
Nucleic Acids Res. 2016 Sep 19;44(16):e131
pubmed: 27270079
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
NPJ Breast Cancer. 2019 Nov 29;5:46
pubmed: 31815182
Nat Med. 2013 Nov;19(11):1450-64
pubmed: 24202397
Nat Biotechnol. 2012 May;30(5):413-21
pubmed: 22544022
Mol Oncol. 2014 Dec;8(8):1588-602
pubmed: 25041824
Nature. 2019 May;569(7757):560-564
pubmed: 31118521
Cancer. 2002 May 15;94(10):2698-705
pubmed: 12173339
Nat Commun. 2019 Nov 20;10(1):5251
pubmed: 31748536
Hum Pathol. 2000 May;31(5):578-83
pubmed: 10836297
Nature. 2002 Oct 10;419(6907):624-9
pubmed: 12374981
Cell Cycle. 2019 Sep;18(17):2110-2123
pubmed: 31290724
Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11428-11436
pubmed: 31061129
Oncotarget. 2018 Dec 14;9(98):37080-37096
pubmed: 30647846
Nature. 2020 Feb;578(7793):94-101
pubmed: 32025018
Genome Med. 2017 Jan 23;9(1):4
pubmed: 28115009
Ann Oncol. 2018 Sep 1;29(9):1948-1954
pubmed: 29917049
Front Oncol. 2019 Aug 28;9:801
pubmed: 31555580
Nat Methods. 2018 Aug;15(8):591-594
pubmed: 30013048
Cell. 2015 Nov 5;163(4):1011-25
pubmed: 26544944
Mol Pharmacol. 2006 Feb;69(2):520-31
pubmed: 16291872
Nature. 2013 Aug 22;500(7463):415-21
pubmed: 23945592
Neurooncol Adv. 2019 Jun 04;1(1):vdz005
pubmed: 32642648
N Engl J Med. 2020 May 28;382(22):2091-2102
pubmed: 32343890
Genome Biol. 2016 Feb 22;17:31
pubmed: 26899170
Nat Genet. 2019 May;51(5):912-919
pubmed: 30988514
Genome Biol. 2019 Nov 14;20(1):240
pubmed: 31727117
Brief Bioinform. 2013 Mar;14(2):178-92
pubmed: 22517427
N Engl J Med. 2016 Aug 4;375(5):443-53
pubmed: 27433846
Cancer Discov. 2018 Feb;8(2):174-183
pubmed: 29247016

Auteurs

Antonio Rodriguez-Calero (A)

Department for BioMedical Research, University of Bern, Bern, Switzerland.
Institute of Pathology, University of Bern, Bern, Switzerland.

John Gallon (J)

Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland.
ORCID: 0000-0002-5328-6298

Dilara Akhoundova (D)

Department for BioMedical Research, University of Bern, Bern, Switzerland.
Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland.

Sina Maletti (S)

Department for BioMedical Research, University of Bern, Bern, Switzerland.

Alison Ferguson (A)

Department for BioMedical Research, University of Bern, Bern, Switzerland.
Department of Oncology, Ludwig Cancer Centre, University of Lausanne, Lausanne, Switzerland.
ORCID: 0000-0002-6491-996X

Joanna Cyrta (J)

Department of Pathology, Institut Curie, University Paris Sciences et Lettres, Paris, France.

Ursula Amstutz (U)

Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Andrea Garofoli (A)

Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.

Viola Paradiso (V)

Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.

Scott A Tomlins (SA)

Departments of Pathology and Urology, University of Michigan Medical School, Ann Arbor, MI, USA.

Ekkehard Hewer (E)

Institute of Pathology, University of Bern, Bern, Switzerland.
Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
ORCID: 0000-0002-9128-0364

Vera Genitsch (V)

Institute of Pathology, University of Bern, Bern, Switzerland.

Achim Fleischmann (A)

Institute of Pathology, University of Bern, Bern, Switzerland.
Institute of Pathology, Cantonal Hospital Thurgau, Münsterlingen, Switzerland.

Erik Vassella (E)

Institute of Pathology, University of Bern, Bern, Switzerland.

Elisabeth J Rushing (EJ)

Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
ORCID: 0000-0001-7616-6320

Rainer Grobholz (R)

Institute of Pathology, Cantonal Hospital Aarau, Aarau, Switzerland.
ORCID: 0000-0002-1901-7967

Ingeborg Fischer (I)

Institute of Pathology, Cantonal Hospital Aarau, Aarau, Switzerland.

Wolfram Jochum (W)

Institute of Pathology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

Gieri Cathomas (G)

Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.

Adeboye O Osunkoya (AO)

Departments of Pathology and Laboratory Medicine, and Urology, Emory University School of Medicine, Atlanta, USA.
ORCID: 0000-0001-5712-8134

Lukas Bubendorf (L)

Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
ORCID: 0000-0001-5970-1803

Holger Moch (H)

Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
ORCID: 0000-0002-7986-2839

George Thalmann (G)

Department of Urology, Inselspital, Bern University Hospital, Bern, Switzerland.

Charlotte K Y Ng (CKY)

Department for BioMedical Research, University of Bern, Bern, Switzerland.
ORCID: 0000-0002-6100-0026

Silke Gillessen (S)

Faculty of Biomedical Sciences, USI, Lugano, Switzerland.
Department of Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom.

Salvatore Piscuoglio (S)

Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland. s.piscuoglio@unibas.ch.
Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland. s.piscuoglio@unibas.ch.
ORCID: 0000-0003-2686-2939

Mark A Rubin (MA)

Department for BioMedical Research, University of Bern, Bern, Switzerland. mark.rubin@dbmr.unibe.ch.
Bern Center for Precision Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. mark.rubin@dbmr.unibe.ch.
ORCID: 0000-0002-8321-9950

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Classifications MeSH

questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Alterations in homologous recombination repair...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Alterations in homologous recombination repair...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Alterations in homologous recombination repair...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Inhibiteurs de poly(ADP-ribose) polymérases › Alterations in homologous recombination repair...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Alterations in homologous recombination repair...
questionsmedicales.fr › Phénomènes génétiques › Recombinaison génétique › Recombinaison homologue › Réparation de l'ADN par recombinaison › Alterations in homologous recombination repair...