@article{d4318d6eb9e14bc685c32d14326ccd4d,
title = "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.",
author = "Feng Liu and Hon, {Gary C.} and Villa, {Genaro R.} and Turner, {Kristen M.} and Shiro Ikegami and Huijun Yang and Zhen Ye and Bin Li and Samantha Kuan and Lee, {Ah Young} and Ciro Zanca and Bowen Wei and Greg Lucey and David Jenkins and Wei Zhang and Barr, {Cathy L.} and Furnari, {Frank B.} and Cloughesy, {Timothy F.} and Yong, {William H.} and Gahman, {Timothy C.} and Shiau, {Andrew K.} and Cavenee, {Webster K.} and Bing Ren and Mischel, {Paul S.}",
note = "Funding Information: The infrared Fluorescent Protein 720 (IRFP720) expression construct was kindly given by Dr. V.V. Verkhusha. This work is supported by the National Institute for Neurological Diseases and Stroke grant NS73831 (to P.S.M.); the Defeat GBM Program of the National Brain Tumor Society and generous donations from the Ziering Family Foundation in memory of Sigi Ziering (to P.S.M. and T.F.C.); the Ben and Catherine Ivy Foundation (to P.S.M., T.F.C., and W.H.Y.); the Ludwig Institute for Cancer Research (to B.R., A.K.S., and T.C.G.); the Cancer Prevention and Research Institute of Texas grant RR140023 (to G.C.H.); UCSD Core Facility Stimulus Funding (to B.R.); the NIH grant R01-NS080939 (to F.B.F.); the National Cancer Institute grant F31CA186668 (to G.R.V.); the Hospital for Sick Children Psychiatric Endowment Fund (to C.L.B.); Art of the Brain (to T.F.C. and W.H.Y.); and the Uncle Kory Foundation (to T.F.C.). W.K.C. is a Fellow of the National Foundation for Cancer Research. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = oct,
day = "15",
doi = "10.1016/j.molcel.2015.09.002",
language = "English (US)",
volume = "60",
pages = "307--318",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",
}