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

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 A. Doyle, Richard Lupat, Jason Li, Jan Schroeder, Meaghan Wall, Stuart Craig, Gretchen Poortinga, Don Cameron, Megan Bywater, Lev KatsMicah D. Gearhart, Vivian J. Bardwell, Ross A. Dickins, Ross D. Hannan, Anthony T. Papenfuss, Ricky W. Johnstone

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish (US)
Article number14581
JournalNature communications
Volume8
DOIs
StatePublished - Mar 6 2017

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© 2017 The Author(s).

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