Liu et al. used integrated epigenome and transcriptome analyses of cell lines, genotyped clinical samples, and The Cancer Genome Analysis data, to show that EGFR mutations remodel the activated enhancer background of GBM to promote aggressive tumor growth through a SOX9 and FOXG1-dependent transcriptional regulatory network in vitro and in vivo. The gene discussed is FOXG1; the disease is glioblastoma.