Sin-Chan, PatrickMumal, IqraSuwal, TannuHo, BenFan, XiaolianSingh, IrtishaDu, YuchenLu, MeiPatel, NeilketTorchia, JonathonPopovski, DeanFouladi, MaryamGuilhamon, PaulHansford, Jordan RLeary, SarahHoffman, Lindsey MMulcahy Levy, Jean MLassaletta, AlvaroSolano-Paez, PalmaRivas, EloyReddy, AlyssaGillespie, G YanceyGupta, NalinVan Meter, Timothy ENakamura, HideoWong, Tai-TongRa, Young-ShinKim, Seung-KiMassimi, LucaGrundy, Richard GFangusaro, JasonJohnston, DonnaChan, JenniferLafay-Cousin, LucieHwang, Eugene IWang, YinCatchpoole, DanielMichaud, JeanEllezam, BenjaminRamanujachar, RamyaLindsay, HollyTaylor, Michael DHawkins, Cynthia EBouffet, EricJabado, NadaSingh, Sheila KKleinman, Claudia LBarsyte-Lovejoy, DaliaLi, Xiao-NanDirks, Peter BLin, Charles YMack, Stephen CRich, Jeremy NHuang, Annie2023-01-252023-01-252019http://hdl.handle.net/10668/14229Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. Our data show that this powerful oncogenic circuit, which entraps an early neural lineage network, is potently abrogated by bromodomain inhibitor JQ1, leading to ETMR cell death.enC19MCETMRLIN28AMYCNbrain tumorcell-cycleepigeneticsmicroRNAsuper-enhancertherapeuticsBiomarkers, TumorBrain NeoplasmsCell CycleCell Transformation, NeoplasticChromosomes, Human, Pair 19Chromosomes, Human, Pair 2DNA Copy Number VariationsEnhancer Elements, GeneticEpigenesis, GeneticGene Expression RegulationGene Regulatory NetworksGenetic Association StudiesGenetic Predisposition to DiseaseHumansMicroRNAsModels, BiologicalMultigene FamilyN-Myc Proto-Oncogene ProteinNeoplasms, Germ Cell and EmbryonalOncogenesRNA-Binding Proteinsresearch article31287992open access10.1016/j.ccell.2019.06.0021878-3686http://www.cell.com/article/S1535610819302934/pdf