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Oncotarget. 2016 May 31;7(22):31681-8. doi: 10.18632/oncotarget.9426.

The impact of the MYB-NFIB fusion proto-oncogene in vivo.

Mikse OR1,2,3, Tchaicha JH1,2,3, Akbay EA1,2,3, Chen L1,2,3, Bronson RT4, Hammerman PS1,2,5, Wong KK1,2,3,6.

Author information

1
Department of Medicine, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
2
Harvard Medical School, Boston, Massachusetts, USA.
3
Ludwig Institute for Cancer, Cambridge, Massachusetts, USA.
4
Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston, Massachusetts, USA.
5
The Broad Institute, Cambridge, Massachusetts, USA.
6
Belfer Institute for Applied Cancer Science, Boston, Massachusetts, USA.

Abstract

Recurrent fusion of the v-myb avian myelobastosis viral oncogene homolog (MYB) and nuclear factor I/B (NFIB) generates the MYB-NFIB transcription factor, which has been detected in a high percentage of individuals with adenoid cystic carcinoma (ACC). To understand the functional role of this fusion protein in carcinogenesis, we generated a conditional mutant transgenic mouse that expresses MYB-NFIB along with p53 mutation in tissues that give rise to ACC: mammary tissue, salivary glands, or systemically in the whole body. Expression of the oncogene in mammary tissue resulted in hyperplastic glands that developed into adenocarcinoma in 27.3% of animals. Systemic expression of the MYB-NFIB fusion caused more rapid development of this breast phenotype, but mice died due to abnormal proliferation in the glomerular compartment of the kidney, which led to development of glomerulonephritis. These findings suggest the MYB-NFIB fusion is oncogenic and treatments targeting this transcription factor may lead to therapeutic responses in ACC patients.

KEYWORDS:

GEMM; MYB-NFIB; adenoid cystic carcinoma; breast; salivary

PMID:
27213588
PMCID:
PMC5077968
DOI:
10.18632/oncotarget.9426
[Indexed for MEDLINE]
Free PMC Article

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