Journal
MOLECULAR CELL
Volume 60, Issue 2, Pages 307-318Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2015.09.002
Keywords
-
Categories
Funding
- National Institute for Neurological Diseases and Stroke grant [NS73831]
- Defeat GBM Program of the National Brain Tumor Society
- Cancer Prevention and Research Institute of Texas grant [RR140023]
- UCSD Core Facility Stimulus Funding
- NIH [R01-NS080939]
- National Cancer Institute [F31CA186668]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available