CHROMATIN LANDSCAPES REVEAL DEVELOPMENTALLY ENCODED TRANSCRIPTIONAL STATES THAT DEFINE GLIOBLASTOMA [ChIP-Seq]

Glioblastoma is an incurable brain cancer characterized by high genetic and pathological heterogeneity. Here we mapped active chromatin landscapes with gene expression, whole-exomes, copy number profiles, and DNA methylomes across 44 glioblastoma stem cell (GSCs) models, 50 primary glioblastomas, and 10 neural stem cells (NSCs) with the goal of identifying essential super enhancer (SE)-associated genes and the core transcription factors that establish them and glioblastoma identity. Glioblastomas segregate with two dominant enhancer profiles that coopt unique developmental transcription factor regulatory programs to enforce tumor identity. From group specific enhancer profiles, we inferred core transcription factors that define subgroup identity. These transcription factors show higher activity in glioblastomas versus normal neural stem cells, are associated with poor clinical outcomes, and are required for glioblastoma growth in vitro and in vivo. Given challenges with genetically-defined targeted therapies for glioblastoma, we propose targeting underlying transcriptional identity may serve as an important therapeutic strategy. Overall design: Dataset consists of active chromatin profiles as measured by H3K27 acetylation ChIP-seq analysis on glioblastoma primary tissue and chromatin derived from glioblastoma stem cells For primary GBM samples, we have 50 GBM samples in total, 46 of which have H3k27ac ChIPseq data, 45 of which have RNAseq data, and 39 of which have methylation data (GBM74 has replicate data). For glioblastoma stem cell samples, we have 44 GSC samples in total, 43 of which have H3k27ac ChIPseq data, 44 of which have RNAseq data, and 41 of which have methylation data. For neural stem cell samples, we have 10 NSC samples in total, 9 of which have H3k27ac ChIPseq data, 9 of which have RNAseq data, and 9 of which have methylation data.