EGFR Mutation Promotes Glioblastoma through Epigenome and Transcription Factor Network Remodeling.
Mol Cell
; 60(2): 307-18, 2015 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-26455392
ABSTRACT
Epidermal growth factor receptor (EGFR) gene amplification and mutations are the most common oncogenic events in glioblastoma (GBM), but the mechanisms by which they promote aggressive tumor growth are not well understood. Here, through integrated epigenome and transcriptome analyses of cell lines, genotyped clinical samples, and TCGA data, we show that EGFR mutations remodel the activated enhancer landscape of GBM, promoting tumorigenesis through a SOX9 and FOXG1-dependent transcriptional regulatory network in vitro and in vivo. The most common EGFR mutation, EGFRvIII, sensitizes GBM cells to the BET-bromodomain inhibitor JQ1 in a SOX9, FOXG1-dependent manner. These results identify the role of transcriptional/epigenetic remodeling in EGFR-dependent pathogenesis and suggest a mechanistic basis for epigenetic therapy.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
/
Glioblastoma
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Epigénesis Genética
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Factores de Transcripción Forkhead
/
Factor de Transcripción SOX9
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Receptores ErbB
/
Proteínas del Tejido Nervioso
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Animals
/
Child
/
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos