Clinical Pathology - Research Publications

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

Lefebure, M ; Tothill, RW ; Kruse, E ; Hawkins, ED ; Shortt, J ; Matthews, GM ; Gregory, GP ; Martin, BP ; Kelly, MJ ; Todorovski, I ; Doyle, MA ; Lupat, R ; Li, J ; Schroeder, J ; Wall, M ; Craig, S ; Poortinga, G ; Cameron, D ; Bywater, M ; Kats, L ; Gearhart, MD ; Bardwell, VJ ; Dickins, RA ; Hannan, RD ; Papenfuss, AT ; Johnstone, RW (NATURE PUBLISHING GROUP, 2017-03-06)

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.