title: The impact of the MYB-NFIB fusion proto-oncogene in vivo.
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.
authors.affiliation: Department of Medicine, Dana Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.|Ludwig Institute for Cancer, Cambridge, Massachusetts, USA.
authors.forename: Oliver R
authors.initials: OR
authors.lastname: Mikse
authors.affiliation: Department of Medicine, Dana Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.|Ludwig Institute for Cancer, Cambridge, Massachusetts, USA.
authors.forename: Jeremy H
authors.initials: JH
authors.lastname: Tchaicha
authors.affiliation: Department of Medicine, Dana Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.|Ludwig Institute for Cancer, Cambridge, Massachusetts, USA.
authors.forename: Esra A
authors.initials: EA
authors.lastname: Akbay
authors.affiliation: Department of Medicine, Dana Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.|Ludwig Institute for Cancer, Cambridge, Massachusetts, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.affiliation: Department of Medicine, Dana Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.|The Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Hammerman
authors.affiliation: Department of Medicine, Dana Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.|Ludwig Institute for Cancer, Cambridge, Massachusetts, USA.|Belfer Institute for Applied Cancer Science, Boston, Massachusetts, USA.
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: C000715470:MAS1 protein, human; C545202:MYB-NFIB fusion protein, human; D015514:Oncogene Proteins, Fusion; D000090063:Proto-Oncogene Mas
keywords: GEMM; MYB-NFIB; adenoid cystic carcinoma; breast; salivary