Journal article
Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene
M Lefebure, RW Tothill, E Kruse, ED Hawkins, J Shortt, GM Matthews, GP Gregory, BP Martin, MJ Kelly, I Todorovski, MA Doyle, R Lupat, J Li, J Schroeder, M Wall, S Craig, G Poortinga, D Cameron, M Bywater, L Kats Show all
Nature Communications | NATURE PUBLISHING GROUP | Published : 2017
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..
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Awarded by National Cancer Institute
Funding Acknowledgements
We thank Charles Mullighan and Ari Melnick for helpful discussion and Jerry Pelletier for providing us with the pCIG-constructs. We thank members of the Peter Mac Molecular Genomics Core Facility for their contribution. We acknowledge the following funding agencies: Leukaemia Foundation of Australia, Arrow Bone Marrow Transplant Foundation, National Health and Medical Research Council Australia, Cancer Council Victoria, Victorian Cancer Agency, Australian Cancer Research Foundation, Peter MacCallum Cancer Centre Foundation, National Institutes of Health.