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

Genetics, Cell Biology and Development (TMED)

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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 (US)
Article number	14581
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14581
State	Published - Mar 6 2017

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Publisher Copyright:
© 2017 The Author(s).

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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

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

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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.}",

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AU - Hawkins, Edwin D.

AU - Shortt, Jake

AU - Matthews, Geoffrey M.

AU - Gregory, Gareth P.

AU - Martin, Benjamin P.

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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.

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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.

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

Abstract

Bibliographical note

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