Transcriptomics,Genomics

Dataset Information

298

EGFR Mutation Promotes Glioblastoma Through Epigenome and Transcription Factor Network Remodeling


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. ChIP-Seq for H3K27ac, H3K4me1, and H3K4me3, and RNA-seq for Glioblastoma (GBM) cells and/or tissues with or without EGFRvIII mutation.

ORGANISM(S): Homo sapiens  

SUBMITTER: Timothy F Cloughesy   Webster K Cavenee  Ah Y Lee  Greg Lucey  Kristen M Turner  Genaro R Villa  Gary C Hon  Samantha Kuan  Bing Ren  Zhen Ye  Frank B Furnari  Wei Zhang  David Jenkins  Feng Liu  Ciro Zanca  Bowen Wei  Paul S Mischel  William H Yong  Cathy L Barr  Bin Li  Huijun Yang  Andrew K Shiau  Paul Mischel  Shiro Ikegami  Timonthy C Gahman 

PROVIDER: E-GEOD-72468 | ArrayExpress | 2015-09-14

SECONDARY ACCESSION(S): SRP063070GSE72468PRJNA294444

REPOSITORIES: GEO, ArrayExpress, ENA

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