EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer

Luke Hughes-Davies; David Huntsman; Margarida Ruas; Francois Fuks; Jacqueline Bye; Suet-Feung Chin; Jonathon Milner; Lindsay A Brown; Forrest Hsu; Blake Gilks; Torsten Nielsen; Michael Schulzer; Stephen Chia; Joseph Ragaz; Anthony Cahn; Lori Linger; Hilal Ozdag; Elena Cattaneo; E.S Jordanova; Edward Schuuring; David S Yu; Ashok Venkitaraman; Bruce Ponder; Aidan Doherty; Samuel Aparicio; David Bentley; Charles Theillet; Chris P Ponting; Carlos Caldas; Tony Kouzarides

doi:10.1016/S0092-8674(03)00930-9

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EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer

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EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer

Luke Hughes-Davies, David Huntsman, Margarida Ruas, Francois Fuks, Jacqueline Bye, Suet-Feung Chin, Jonathon Milner, Lindsay A Brown, Forrest Hsu, Blake Gilks, …

Cell, Vol.115(5), pp.523-535

26/11/2003

DOI: https://doi.org/10.1016/S0092-8674(03)00930-9

PMID: 14651845

Résumé

The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer. EMSY is capable of silencing the activation potential of BRCA2 exon 3, associates with chromatin regulators HP1β and BS69, and localizes to sites of repair following DNA damage. EMSY maps to chromosome 11q13.5, a region known to be involved in breast and ovarian cancer. We show that the EMSY gene is amplified almost exclusively in sporadic breast cancer (13%) and higher-grade ovarian cancer (17%). In addition, EMSY amplification is associated with worse survival, particularly in node-negative breast cancer, suggesting that it may be of prognostic value. The remarkable clinical overlap between sporadic EMSY amplification and familial BRCA2 deletion implicates a BRCA2 pathway in sporadic breast and ovarian cancer.

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Titre: EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer
Créateurs - sans rôle: Luke Hughes-Davies - Cancer Research UK/Wellcome Trust Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QR, United Kingdom
David Huntsman - Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Center at the Vancouver General Hospital, Department of Pathology, British Columbia Cancer Agency, and the University of British Columbia, Room 509, JBRC, 2660 Oak Street, Vancouver, British Columbia V6H 3Z6, Canada
Margarida Ruas - Cancer Research UK/Wellcome Trust Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QR, United Kingdom
Francois Fuks - Cancer Research UK/Wellcome Trust Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QR, United Kingdom
Jacqueline Bye - The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom
Suet-Feung Chin - Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, United Kingdom
Jonathon Milner - Cancer Research UK/Wellcome Trust Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QR, United Kingdom
Lindsay A Brown - Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Center at the Vancouver General Hospital, Department of Pathology, British Columbia Cancer Agency, and the University of British Columbia, Room 509, JBRC, 2660 Oak Street, Vancouver, British Columbia V6H 3Z6, Canada
Forrest Hsu - Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Center at the Vancouver General Hospital, Department of Pathology, British Columbia Cancer Agency, and the University of British Columbia, Room 509, JBRC, 2660 Oak Street, Vancouver, British Columbia V6H 3Z6, Canada
Blake Gilks - Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Center at the Vancouver General Hospital, Department of Pathology, British Columbia Cancer Agency, and the University of British Columbia, Room 509, JBRC, 2660 Oak Street, Vancouver, British Columbia V6H 3Z6, Canada
Torsten Nielsen - Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Center at the Vancouver General Hospital, Department of Pathology, British Columbia Cancer Agency, and the University of British Columbia, Room 509, JBRC, 2660 Oak Street, Vancouver, British Columbia V6H 3Z6, Canada
Michael Schulzer - Department of Statistics and Medicine, University of British Columbia, 221 Wesbrook Mall, Vancouver, British Columbia V6T 2B5, Canada
Stephen Chia - Department of Medical Oncology, British Columbia Cancer, 600 West 10th Avenue, Vancouver, British Columbia, V5Z 4E6, Canada
Joseph Ragaz - Department of Medical Oncology, British Columbia Cancer, 600 West 10th Avenue, Vancouver, British Columbia, V5Z 4E6, Canada
Anthony Cahn - The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom
Lori Linger - Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, United Kingdom
Hilal Ozdag - Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, United Kingdom
Elena Cattaneo - Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, United Kingdom
E.S Jordanova - Department of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
Edward Schuuring - Department of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
David S Yu - Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, United Kingdom
Ashok Venkitaraman - Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, United Kingdom
Bruce Ponder - Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, United Kingdom
Aidan Doherty - Cambridge Institute for Medical Research, Cambridge, CB2 2XY, United Kingdom
Samuel Aparicio - Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, United Kingdom
David Bentley - The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom
Charles Theillet - INSERM EMI 229, Centre Val d'Aurelle, Montpellier, France
Chris P Ponting - MRC Functional Genetics Unit, University of Oxford, Oxford OX1 3QX, United Kingdom
Carlos Caldas - University of Cambridge
Tony Kouzarides - Cancer Research UK/Wellcome Trust Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QR, United Kingdom
Détails de publication: Cell, Vol.115(5), pp.523-535
Éditeur: Elsevier Inc
Nombre de pages: 13
Identifiants: 99162929309311
Unité académique: Institut de Recherche en Cancérologie de Montpellier - IRCM
Langue: English
Type de ressource: Journal article