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.
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Marcus
authors.initials: M
authors.lastname: Lefebure
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia.|Department of Pathology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tothill
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kruse
authors.affiliation: The Walter Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Hawkins
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing &Health Sciences, Clayton, Victoria 3168, Australia.
authors.forename: Jake
authors.initials: J
authors.lastname: Shortt
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Matthews
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Gareth P
authors.initials: GP
authors.lastname: Gregory
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Martin
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Madison J
authors.initials: MJ
authors.lastname: Kelly
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Izabela
authors.initials: I
authors.lastname: Todorovski
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Doyle
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Lupat
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Li
authors.affiliation: The Walter Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Jan
authors.initials: J
authors.lastname: Schroeder
authors.affiliation: Victorian Cancer Cytogenetics Service, St Vincent's Hospital, Fitzroy, Victoria 3065, Australia.|Department of Medicine, St Vincent's Hospital, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Wall
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Craig
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Poortinga
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Don
authors.initials: D
authors.lastname: Cameron
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Megan
authors.initials: M
authors.lastname: Bywater
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Lev
authors.initials: L
authors.lastname: Kats
authors.affiliation: Developmental Biology Center, Masonic Cancer Center, and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Micah D
authors.initials: MD
authors.lastname: Gearhart
authors.affiliation: Developmental Biology Center, Masonic Cancer Center, and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Vivian J
authors.initials: VJ
authors.lastname: Bardwell
authors.affiliation: Australian Centre for Blood Diseases, Monash University, AMREP Building, Commercial Road, The Alfred Hospital, Melbourne, Victoria 3004, Australia.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Dickins
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|Cancer Biology and Therapeutics Department, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 0200, Australia.
authors.forename: Ross D
authors.initials: RD
authors.lastname: Hannan
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia.|The Walter Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Papenfuss
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Ricky W
authors.initials: RW
authors.lastname: Johnstone
mesh_terms: D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D064113:CRISPR-Cas Systems; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D000072669:Gene Editing; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D053614:Janus Kinase 2 / Q000235:genetics / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000276:immunology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics* / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology; D000073336:Whole Genome Sequencing
chemical_list: C553467:Bcor protein, mouse; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; C000628667:Trp53 protein, mouse; D016159:Tumor Suppressor Protein p53; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)