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Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene

Author

Listed:
  • Marcus Lefebure

    (The Peter MacCallum Cancer Centre
    University of Melbourne)

  • Richard W. Tothill

    (The Peter MacCallum Cancer Centre
    University of Melbourne
    University of Melbourne)

  • Elizabeth Kruse

    (The Peter MacCallum Cancer Centre)

  • Edwin D. Hawkins

    (The Walter Eliza Hall Institute of Medical Research)

  • Jake Shortt

    (The Peter MacCallum Cancer Centre
    School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing & Health Sciences)

  • Geoffrey M. Matthews

    (Dana Farber Cancer Institute)

  • Gareth P. Gregory

    (The Peter MacCallum Cancer Centre)

  • Benjamin P. Martin

    (The Peter MacCallum Cancer Centre)

  • Madison J. Kelly

    (The Peter MacCallum Cancer Centre)

  • Izabela Todorovski

    (The Peter MacCallum Cancer Centre)

  • Maria A. Doyle

    (The Peter MacCallum Cancer Centre)

  • Richard Lupat

    (The Peter MacCallum Cancer Centre)

  • Jason Li

    (The Peter MacCallum Cancer Centre)

  • Jan Schroeder

    (The Walter Eliza Hall Institute of Medical Research)

  • Meaghan Wall

    (Victorian Cancer Cytogenetics Service, St Vincent’s Hospital
    St Vincent’s Hospital, University of Melbourne)

  • Stuart Craig

    (The Peter MacCallum Cancer Centre)

  • Gretchen Poortinga

    (The Peter MacCallum Cancer Centre)

  • Don Cameron

    (The Peter MacCallum Cancer Centre)

  • Megan Bywater

    (The Peter MacCallum Cancer Centre)

  • Lev Kats

    (The Peter MacCallum Cancer Centre
    University of Melbourne)

  • Micah D. Gearhart

    (Developmental Biology Center, Masonic Cancer Center, Cell Biology, and Development, University of Minnesota)

  • Vivian J. Bardwell

    (Developmental Biology Center, Masonic Cancer Center, Cell Biology, and Development, University of Minnesota)

  • Ross A. Dickins

    (Australian Centre for Blood Diseases, Monash University)

  • Ross D. Hannan

    (The Peter MacCallum Cancer Centre
    John Curtin School of Medical Research, Australian National University)

  • Anthony T. Papenfuss

    (The Peter MacCallum Cancer Centre
    University of Melbourne
    The Walter Eliza Hall Institute of Medical Research)

  • Ricky W. Johnstone

    (The Peter MacCallum Cancer Centre
    University of Melbourne)

Abstract

The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor. These findings challenge the assumed two-hit model of Eμ-Myc lymphoma and demonstrate a functional in vivo role for Bcor in suppressing tumorigenesis.

Suggested Citation

  • Marcus Lefebure & Richard W. Tothill & Elizabeth Kruse & Edwin D. Hawkins & Jake Shortt & Geoffrey M. Matthews & Gareth P. Gregory & Benjamin P. Martin & Madison J. Kelly & Izabela Todorovski & Maria , 2017. "Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14581
    DOI: 10.1038/ncomms14581
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