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Genomic characterisation of E?-Myc mouse lymphomas identifies Bcor as a Myc
co-operative tumour-suppressor gene
#MMPMID28262675
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
Nat Commun
2017[Mar]; 8
(?): 14581
PMID28262675
show ga
The E?-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 E?-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 E?-Myc lymphoma and demonstrate a functional in vivo role for Bcor in
suppressing tumorigenesis.
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