| Literature DB >> 26455392 |
Feng Liu1, Gary C Hon1, Genaro R Villa2, Kristen M Turner1, Shiro Ikegami1, Huijun Yang1, Zhen Ye1, Bin Li1, Samantha Kuan1, Ah Young Lee1, Ciro Zanca1, Bowen Wei3, Greg Lucey3, David Jenkins1, Wei Zhang4, Cathy L Barr5, Frank B Furnari6, Timothy F Cloughesy3, William H Yong3, Timothy C Gahman1, Andrew K Shiau1, Webster K Cavenee7, Bing Ren8, Paul S Mischel9.
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.Entities:
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Year: 2015 PMID： 26455392 PMCID： PMC4609298 DOI： 10.1016/j.molcel.2015.09.002
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970