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 Kats; Micah D. Gearhart; Vivian J. Bardwell; Ross A. Dickins; Ross D. Hannan; Anthony T. Papenfuss; Ricky W. Johnstone

doi:10.1038/ncomms14581

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 Kats

Micah D. Gearhart, Vivian J. Bardwell, Ross A. Dickins, Ross D. Hannan, Anthony T. Papenfuss, Ricky W. Johnstone

Research output: Contribution to journal › Article › peer-review

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 language	English
Article number	14581
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14581
Publication status	Published - 6 Mar 2017
Externally published	Yes

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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 Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene. Nature Communications, 8, Article 14581. https://doi.org/10.1038/ncomms14581

@article{04398f0970a142f1a544f91c99a1295d,

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

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.",

author = "Marcus Lefebure and Tothill, \{Richard W.\} and Elizabeth Kruse and Hawkins, \{Edwin D.\} and Jake Shortt and Matthews, \{Geoffrey M.\} and Gregory, \{Gareth P.\} and Martin, \{Benjamin P.\} and Kelly, \{Madison J.\} and Izabela Todorovski and Doyle, \{Maria A.\} and Richard Lupat and Jason Li and Jan Schroeder and Meaghan Wall and Stuart Craig and Gretchen Poortinga and Don Cameron and Megan Bywater and Lev Kats and Gearhart, \{Micah D.\} and Bardwell, \{Vivian J.\} and Dickins, \{Ross A.\} and Hannan, \{Ross D.\} and Papenfuss, \{Anthony T.\} and Johnstone, \{Ricky W.\}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = mar,

day = "6",

doi = "10.1038/ncomms14581",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

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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 2017, 'Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene', Nature Communications, vol. 8, 14581. https://doi.org/10.1038/ncomms14581

TY - JOUR

T1 - Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene

AU - Lefebure, Marcus

AU - Tothill, Richard W.

AU - Kruse, Elizabeth

AU - Hawkins, Edwin D.

AU - Shortt, Jake

AU - Matthews, Geoffrey M.

AU - Gregory, Gareth P.

AU - Martin, Benjamin P.

AU - Kelly, Madison J.

AU - Todorovski, Izabela

AU - Doyle, Maria A.

AU - Lupat, Richard

AU - Li, Jason

AU - Schroeder, Jan

AU - Wall, Meaghan

AU - Craig, Stuart

AU - Poortinga, Gretchen

AU - Cameron, Don

AU - Bywater, Megan

AU - Kats, Lev

AU - Gearhart, Micah D.

AU - Bardwell, Vivian J.

AU - Dickins, Ross A.

AU - Hannan, Ross D.

AU - Papenfuss, Anthony T.

AU - Johnstone, Ricky W.

PY - 2017/3/6

Y1 - 2017/3/6

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85014614477

U2 - 10.1038/ncomms14581

DO - 10.1038/ncomms14581

M3 - Article

C2 - 28262675

AN - SCOPUS:85014614477

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 14581

ER -

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

Abstract

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