2023
Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Zhao S, Mekbib K, van der Ent M, Allington G, Prendergast A, Chau J, Smith H, Shohfi J, Ocken J, Duran D, Furey C, Hao L, Duy P, Reeves B, Zhang J, Nelson-Williams C, Chen D, Li B, Nottoli T, Bai S, Rolle M, Zeng X, Dong W, Fu P, Wang Y, Mane S, Piwowarczyk P, Fehnel K, See A, Iskandar B, Aagaard-Kienitz B, Moyer Q, Dennis E, Kiziltug E, Kundishora A, DeSpenza T, Greenberg A, Kidanemariam S, Hale A, Johnston J, Jackson E, Storm P, Lang S, Butler W, Carter B, Chapman P, Stapleton C, Patel A, Rodesch G, Smajda S, Berenstein A, Barak T, Erson-Omay E, Zhao H, Moreno-De-Luca A, Proctor M, Smith E, Orbach D, Alper S, Nicoli S, Boggon T, Lifton R, Gunel M, King P, Jin S, Kahle K. Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations. Nature Communications 2023, 14: 7452. PMID: 37978175, PMCID: PMC10656524, DOI: 10.1038/s41467-023-43062-z.Peer-Reviewed Original ResearchConceptsEphrin receptor B4Galen malformationBrain arteriovenous malformationsP120 RasGAPTransmitted variantsArteriovenous malformationsDe novo variantsSingle-cell transcriptomesSignificant burdenCerebrovascular developmentIntegrative genomic analysisEndothelial cellsVenous networkAdditional probandsMalformationsNovo variantsMissense variantsGenomic analysisDevelopmental angiogenesisVascular developmentDamaging variantsVeinRasGAPIntegrated analysisPatientsSuper-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas
Youngblood M, Erson-Omay Z, Li C, Najem H, Coșkun S, Tyrtova E, Montejo J, Miyagishima D, Barak T, Nishimura S, Harmancı A, Clark V, Duran D, Huttner A, Avşar T, Bayri Y, Schramm J, Boetto J, Peyre M, Riche M, Goldbrunner R, Amankulor N, Louvi A, Bilgüvar K, Pamir M, Özduman K, Kilic T, Knight J, Simon M, Horbinski C, Kalamarides M, Timmer M, Heimberger A, Mishra-Gorur K, Moliterno J, Yasuno K, Günel M. Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas. Nature Communications 2023, 14: 6279. PMID: 37805627, PMCID: PMC10560290, DOI: 10.1038/s41467-023-41926-y.Peer-Reviewed Original Research
2017
Integrated genomic analyses of de novo pathways underlying atypical meningiomas
Harmancı AS, Youngblood MW, Clark VE, Coşkun S, Henegariu O, Duran D, Erson-Omay EZ, Kaulen LD, Lee TI, Abraham BJ, Simon M, Krischek B, Timmer M, Goldbrunner R, Omay SB, Baranoski J, Baran B, Carrión-Grant G, Bai H, Mishra-Gorur K, Schramm J, Moliterno J, Vortmeyer AO, Bilgüvar K, Yasuno K, Young RA, Günel M. Integrated genomic analyses of de novo pathways underlying atypical meningiomas. Nature Communications 2017, 8: 14433. PMID: 28195122, PMCID: PMC5316884, DOI: 10.1038/ncomms14433.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBrain NeoplasmsCell Transformation, NeoplasticChromosomal InstabilityCluster AnalysisDNA MethylationE2F2 Transcription FactorEnhancer of Zeste Homolog 2 ProteinEpigenomicsExomeForkhead Box Protein M1Gene Expression ProfilingGene Expression Regulation, NeoplasticGene Regulatory NetworksGene SilencingGenes, Neurofibromatosis 2GenomeGenomicsGenotyping TechniquesHuman Embryonic Stem CellsHumansJumonji Domain-Containing Histone DemethylasesMeningeal NeoplasmsMeningiomaMolecular Probe TechniquesMutationPhenotypePolycomb Repressive Complex 2Promoter Regions, GeneticRNA, MessengerSequence AnalysisSignal TransductionSMARCB1 ProteinTranscriptomeConceptsPolycomb repressive complex 2Human embryonic stem cellsRepressive complex 2Integrated genomic analysisEmbryonic stem cellsDe novo pathwayH3K27me3 signalsTranscriptional networksPRC2 complexEpigenomic analysisCellular statesCatalytic subunitGenomic analysisGenomic instabilityHypermethylated phenotypeGenomic landscapeNovo pathwayDisplay lossStem cellsPotential therapeutic targetExhibit upregulationPromoter mutationsTherapeutic targetMutationsComplexes 2