EGFR Mutation Promotes Glioblastoma through Epigenome and Transcription Factor Network Remodeling.
Mol Cell
; 60(2): 307-18, 2015 Oct 15.
Article
em 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
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Glioblastoma
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Epigênese Genética
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Fatores de Transcrição Forkhead
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Fatores de Transcrição SOX9
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Receptores ErbB
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Animals
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Child
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article