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

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Lefebure, M; Tothill, RW; Kruse, E; Hawkins, ED; Shortt, J; Matthews, GM; Gregory, GP; Martin, BP; Kelly, MJ; Todorovski, I; ...Date
2017-03-06Source Title
Nature CommunicationsPublisher
NATURE PUBLISHING GROUPUniversity 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 OncologyMedical Biology (W.E.H.I.)
Clinical Pathology
Bio21
Computing and Information Systems
Medicine and Radiology
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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 AccessAbstract
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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