EGAGenomicsN/Ahttps://ega-archive.org/datasets/EGAD0000100188782EGA dataset EGAD00001001887EGAGliomas represent approximately 30% of all central nervous system tumors and 80% of malignant brain tumors. To understand the molecular mechanisms underlying the malignant progression of low-grade gliomas with mutations in IDH1 (encoding isocitrate dehydrogenase 1), we studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples to their lower-grade counterparts. Integrated genomic analyses, including whole-exome sequencing and copy number, gene expression and DNA methylation profiling, demonstrated nonlinear clonal expansion of the original tumors and identified oncogenic pathways driving progression. These include activation of the MYC and RTK-RAS-PI3K pathways and upregulation of the FOXM1- and E2F2-mediated cell cycle transitions, as well as epigenetic silencing of developmental transcription factor genes bound by Polycomb repressive complex 2 in human embryonic stem cells. Our results not only provide mechanistic insight into the genetic and epigenetic mechanisms driving glioma progression but also identify inhibition of the bromodomain and extraterminal (BET) family as a potential therapeutic approach.Integrated genomic characterization of IDH1-mutant glioma malignant progression.Bai Hanwen H, Harmancı Akdes Serin AS, Erson-Omay E Zeynep EZ, Li Jie J, Coşkun Süleyman S, Simon Matthias M, Krischek Boris B, Özduman Koray K, Omay S Bülent SB, Sorensen Eric A EA, Turcan Şevin Ş, Bakırcığlu Mehmet M, Carrión-Grant Geneive G, Murray Phillip B PB, Clark Victoria E VE, Ercan-Sencicek A Gulhan AG, Knight James J, Sencar Leman L, Altınok Selin S, Kaulen Leon D LD, Gülez Burcu B, Timmer Marco M, Schramm Johannes J, Mishra-Gorur Ketu K, Henegariu Octavian O, Moliterno Jennifer J, Louvi Angeliki A, Chan Timothy A TA, Tannheimer Stacey L SL, Pamir M Necmettin MN, Vortmeyer Alexander O AO, Bilguvar Kaya K, Yasuno Katsuhito K, Günel Murat Mfalseena-DATASET-Yale-19-01-2016-18:21:27:507-133 - samplesExome sequencing VCF files describing mutations during glioma progression.2017-07-26 15:39:25EGAD00001001887960626618343EGAC00001000406EGAS00001001588