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

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    Author
    Lefebure, M; Tothill, RW; Kruse, E; Hawkins, ED; Shortt, J; Matthews, GM; Gregory, GP; Martin, BP; Kelly, MJ; Todorovski, I; ...
    Date
    2017-03-06
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Doyle, Maria; Tothill, Richard; Shortt, Jake; Li, Jason; Poortinga, Gretchen; Kats, Lev; Hannan, Ross; Papenfuss, Anthony; Johnstone, Ricky; Hawkins, Edwin; ...
    Affiliation
    Sir Peter MacCallum Department of Oncology
    Medical Biology (W.E.H.I.)
    Clinical Pathology
    Bio21
    Computing and Information Systems
    Medicine and Radiology
    Metadata
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    Document Type
    Journal Article
    Citations
    Lefebure, M., Tothill, R. W., Kruse, E., Hawkins, E. D., Shortt, J., Matthews, G. M., Gregory, G. P., Martin, B. P., Kelly, M. J., Todorovski, I., Doyle, M. A., Lupat, R., Li, J., Schroeder, J., Wall, M., Craig, S., Poortinga, G., Cameron, D., Bywater, M. ,... Johnstone, R. W. (2017). Genomic characterisation of E mu-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene. NATURE COMMUNICATIONS, 8 (1), pp.1-10. https://doi.org/10.1038/ncomms14581.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/258287
    DOI
    10.1038/ncomms14581
    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.

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