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A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor.

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dc.contributor.authorSin-Chan, Patrick
dc.contributor.authorMumal, Iqra
dc.contributor.authorSuwal, Tannu
dc.contributor.authorHo, Ben
dc.contributor.authorFan, Xiaolian
dc.contributor.authorSingh, Irtisha
dc.contributor.authorDu, Yuchen
dc.contributor.authorLu, Mei
dc.contributor.authorPatel, Neilket
dc.contributor.authorTorchia, Jonathon
dc.contributor.authorPopovski, Dean
dc.contributor.authorFouladi, Maryam
dc.contributor.authorGuilhamon, Paul
dc.contributor.authorHansford, Jordan R
dc.contributor.authorLeary, Sarah
dc.contributor.authorHoffman, Lindsey M
dc.contributor.authorMulcahy Levy, Jean M
dc.contributor.authorLassaletta, Alvaro
dc.contributor.authorSolano-Paez, Palma
dc.contributor.authorRivas, Eloy
dc.contributor.authorReddy, Alyssa
dc.contributor.authorGillespie, G Yancey
dc.contributor.authorGupta, Nalin
dc.contributor.authorVan Meter, Timothy E
dc.contributor.authorNakamura, Hideo
dc.contributor.authorWong, Tai-Tong
dc.contributor.authorRa, Young-Shin
dc.contributor.authorKim, Seung-Ki
dc.contributor.authorMassimi, Luca
dc.contributor.authorGrundy, Richard G
dc.contributor.authorFangusaro, Jason
dc.contributor.authorJohnston, Donna
dc.contributor.authorChan, Jennifer
dc.contributor.authorLafay-Cousin, Lucie
dc.contributor.authorHwang, Eugene I
dc.contributor.authorWang, Yin
dc.contributor.authorCatchpoole, Daniel
dc.contributor.authorMichaud, Jean
dc.contributor.authorEllezam, Benjamin
dc.contributor.authorRamanujachar, Ramya
dc.contributor.authorLindsay, Holly
dc.contributor.authorTaylor, Michael D
dc.contributor.authorHawkins, Cynthia E
dc.contributor.authorBouffet, Eric
dc.contributor.authorJabado, Nada
dc.contributor.authorSingh, Sheila K
dc.contributor.authorKleinman, Claudia L
dc.contributor.authorBarsyte-Lovejoy, Dalia
dc.contributor.authorLi, Xiao-Nan
dc.contributor.authorDirks, Peter B
dc.contributor.authorLin, Charles Y
dc.contributor.authorMack, Stephen C
dc.contributor.authorRich, Jeremy N
dc.contributor.authorHuang, Annie
dc.date.accessioned2023-01-25T13:36:32Z
dc.date.available2023-01-25T13:36:32Z
dc.date.issued2019
dc.description.abstractEmbryonal 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.
dc.identifier.doi10.1016/j.ccell.2019.06.002
dc.identifier.essn1878-3686
dc.identifier.pmid31287992
dc.identifier.unpaywallURLhttp://www.cell.com/article/S1535610819302934/pdf
dc.identifier.urihttp://hdl.handle.net/10668/14229
dc.issue.number1
dc.journal.titleCancer cell
dc.journal.titleabbreviationCancer Cell
dc.language.isoen
dc.organizationHospital Universitario Virgen del Rocío
dc.organizationHospital Universitario Virgen del Rocío
dc.page.number51-67.e7
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.rights.accessRightsopen access
dc.subjectC19MC
dc.subjectETMR
dc.subjectLIN28A
dc.subjectMYCN
dc.subjectbrain tumor
dc.subjectcell-cycle
dc.subjectepigenetics
dc.subjectmicroRNA
dc.subjectsuper-enhancer
dc.subjecttherapeutics
dc.subject.meshBiomarkers, Tumor
dc.subject.meshBrain Neoplasms
dc.subject.meshCell Cycle
dc.subject.meshCell Transformation, Neoplastic
dc.subject.meshChromosomes, Human, Pair 19
dc.subject.meshChromosomes, Human, Pair 2
dc.subject.meshDNA Copy Number Variations
dc.subject.meshEnhancer Elements, Genetic
dc.subject.meshEpigenesis, Genetic
dc.subject.meshGene Expression Regulation
dc.subject.meshGene Regulatory Networks
dc.subject.meshGenetic Association Studies
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshHumans
dc.subject.meshMicroRNAs
dc.subject.meshModels, Biological
dc.subject.meshMultigene Family
dc.subject.meshN-Myc Proto-Oncogene Protein
dc.subject.meshNeoplasms, Germ Cell and Embryonal
dc.subject.meshOncogenes
dc.subject.meshRNA-Binding Proteins
dc.titleA C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number36
dspace.entity.typePublication

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