Featured Publications
Genomic profiling of sporadic multiple meningiomas
Erson-Omay EZ, Vetsa S, Vasandani S, Barak T, Nadar A, Marianayagam NJ, Yalcin K, Miyagishima D, Aguilera SM, Robert S, Mishra-Gorur K, Fulbright RK, McGuone D, Günel M, Moliterno J. Genomic profiling of sporadic multiple meningiomas. BMC Medical Genomics 2022, 15: 112. PMID: 35568945, PMCID: PMC9107270, DOI: 10.1186/s12920-022-01258-0.Peer-Reviewed Original ResearchConceptsGrade IComprehensive next-generation sequencingMonoclonal originClinical management strategiesPrior radiation exposureRelevant clinical dataMajority of tumorsInter-tumoral heterogeneitySurgical resectionClinical behaviorGrade IIClinical dataFamily historyMultiple meningiomasGrade I.Same patientMonoclonal expansionPatientsClonal formationBilateral meningiomasMeningiomasIndividual tumorsTumorsPatient behavesGenomic profilingGenomic Analysis of Non-NF2 Meningiomas Reveals Mutations in TRAF7, KLF4, AKT1, and SMO
Clark VE, Erson-Omay EZ, Serin A, Yin J, Cotney J, Özduman K, Avşar T, Li J, Murray PB, Henegariu O, Yilmaz S, Günel JM, Carrión-Grant G, Yılmaz B, Grady C, Tanrıkulu B, Bakırcıoğlu M, Kaymakçalan H, Caglayan AO, Sencar L, Ceyhun E, Atik AF, Bayri Y, Bai H, Kolb LE, Hebert RM, Omay SB, Mishra-Gorur K, Choi M, Overton JD, Holland EC, Mane S, State MW, Bilgüvar K, Baehring JM, Gutin PH, Piepmeier JM, Vortmeyer A, Brennan CW, Pamir MN, Kılıç T, Lifton RP, Noonan JP, Yasuno K, Günel M. Genomic Analysis of Non-NF2 Meningiomas Reveals Mutations in TRAF7, KLF4, AKT1, and SMO. Science 2013, 339: 1077-1080. PMID: 23348505, PMCID: PMC4808587, DOI: 10.1126/science.1233009.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBrain NeoplasmsChromosomes, Human, Pair 22DNA Mutational AnalysisFemaleGenes, Neurofibromatosis 2Genomic InstabilityGenomicsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMeningeal NeoplasmsMeningiomaMiddle AgedMutationNeoplasm GradingProto-Oncogene Proteins c-aktReceptors, G-Protein-CoupledSmoothened ReceptorTumor Necrosis Factor Receptor-Associated Peptides and ProteinsSomatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis
Erson-Omay EZ, Çağlayan AO, Schultz N, Weinhold N, Omay SB, Özduman K, Köksal Y, Li J, Serin Harmancı A, Clark V, Carrión-Grant G, Baranoski J, Çağlar C, Barak T, Coşkun S, Baran B, Köse D, Sun J, Bakırcıoğlu M, Moliterno Günel J, Pamir MN, Mishra-Gorur K, Bilguvar K, Yasuno K, Vortmeyer A, Huttner AJ, Sander C, Günel M. Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis. Neuro-Oncology 2015, 17: 1356-1364. PMID: 25740784, PMCID: PMC4578578, DOI: 10.1093/neuonc/nov027.Peer-Reviewed Original ResearchConceptsHigh-grade gliomasSomatic POLE mutationsPOLE mutationsMalignant high-grade gliomasLonger progression-free survivalProgression-free survivalSomatic mutationsOverall survivalPediatric patientsBetter prognosisClinical featuresImproved prognosisClinical behaviorImmune cellsBizarre cellsAggressive formGlioblastoma multiformeDisease pathophysiologyMolecular subgroupsHomozygous germline mutationGermline mutationsPrognosisGlioma subtypesComprehensive genomic analysisDistinct subgroupsLongitudinal analysis of treatment-induced genomic alterations in gliomas
Erson-Omay EZ, Henegariu O, Omay SB, Harmancı AS, Youngblood MW, Mishra-Gorur K, Li J, Özduman K, Carrión-Grant G, Clark VE, Çağlar C, Bakırcıoğlu M, Pamir MN, Tabar V, Vortmeyer AO, Bilguvar K, Yasuno K, DeAngelis LM, Baehring JM, Moliterno J, Günel M. Longitudinal analysis of treatment-induced genomic alterations in gliomas. Genome Medicine 2017, 9: 12. PMID: 28153049, PMCID: PMC5290635, DOI: 10.1186/s13073-017-0401-9.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsChromosome AberrationsCombined Modality TherapyDisease ProgressionDNA Mismatch RepairDNA Mutational AnalysisDNA, NeoplasmExomeFemaleGeneral SurgeryGenome, HumanGenomicsGlioblastomaHumansImmunotherapyLongitudinal StudiesMiddle AgedMutationNeoplasm Recurrence, LocalPrecision MedicineRadiotherapyTreatment OutcomeConceptsWhole-exome sequencingMismatch repair deficiencyImmune checkpoint inhibitionMalignant brain tumorsMolecular changesLongitudinal analysisMedian survivalCheckpoint inhibitionSubsequent recurrenceMaximal resectionStandard treatmentBackgroundGlioblastoma multiformeBrain tumorsTumor-normal pairsFavorable responsePrimary GBMIndividual tumorsConclusionsOur studyPrecision therapyPersonalized treatmentGenomic profilingRepair deficiencyGenomic alterationsGenomic profilesTherapyHypermutated phenotype in gliosarcoma of the spinal cord
Hong CS, Kuzmik GA, Kundishora AJ, Elsamadicy AA, Koo AB, McGuone D, Blondin NA, DiLuna ML, Erson-Omay EZ. Hypermutated phenotype in gliosarcoma of the spinal cord. Npj Precision Oncology 2021, 5: 8. PMID: 33580181, PMCID: PMC7881101, DOI: 10.1038/s41698-021-00143-w.Peer-Reviewed Original ResearchSpinal cordWhole-exome sequencingLow-grade brain gliomasVariant of glioblastomaLow-grade gliomasTumor anteriorAdjuvant radiationNeurological deficitsSomatic single nucleotide variationsPoor prognosisGrade gliomasTemozolomide treatmentBrain gliomasGliosarcomaMicrosatellite stabilityCordSomatic mutationsHypermutator phenotypeGliomasComprehensive genetic characterizationGenomic mechanismsSingle nucleotide variationsPhenotypeFirst reportPathway genesGenetic characterization of an aggressive optic nerve pilocytic glioma
Hong CS, Fliney G, Fisayo A, An Y, Gopal PP, Omuro A, Pointdujour-Lim R, Erson-Omay EZ, Omay SB. Genetic characterization of an aggressive optic nerve pilocytic glioma. Brain Tumor Pathology 2020, 38: 59-63. PMID: 33098465, PMCID: PMC7585354, DOI: 10.1007/s10014-020-00383-x.Peer-Reviewed Original ResearchConceptsOptic nerve gliomaLeft optic nerve sheathLeft-sided visual lossSporadic adult casesOptic nerve sheathNeurofibromatosis type 1 syndromeType 1 syndromeWhole-exome sequencingEmpiric managementVisual lossFocal radiotherapyOptic nervePediatric populationNerve sheathOpen biopsyAdult casesBiopsy specimenBenign histopathologyClinical prognosticationPilocytic astrocytomaComplex tumorsActionable targetsVisual pathwayAdult populationTumor progression
2024
Variations in the genomic profiles and clinical behavior of meningioma by racial and ethnic group.
Tabor J, Dincer A, O'Brien J, Lei H, Vetsa S, Vasandani S, Jalal M, Yalcin K, Morales-Valero S, Marianayagam N, Alanya H, Elsamadicy A, Millares Chavez M, Aguilera S, Mishra-Gorur K, McGuone D, Fulbright R, Jin L, Erson-Omay E, Günel M, Moliterno J. Variations in the genomic profiles and clinical behavior of meningioma by racial and ethnic group. Journal Of Neurosurgery 2024, 141: 664-672. PMID: 38518289, DOI: 10.3171/2024.1.jns231633.Peer-Reviewed Original ResearchBlack patientsSporadic meningiomasClinical outcomesGenomic profilingClinical behavior of meningiomasShorter progression-free survivalAnterior skull base tumorsClinical data of patientsHispanic patientsProgression-free survivalChromosome 1p deletionBehavior of meningiomasIncreased recurrence rateRate of recurrenceSkull base tumorsData of patientsSomatic driver mutationsNon-Black patientsShorter PFSOverall survivalAggressive meningiomasTRAF7 mutationsIntracranial meningiomasMeningioma resectionNon-black group
2023
Application of novel PACS-based informatics platform to identify imaging based predictors of CDKN2A allelic status in glioblastomas
Tillmanns N, Lost J, Tabor J, Vasandani S, Vetsa S, Marianayagam N, Yalcin K, Erson-Omay E, von Reppert M, Jekel L, Merkaj S, Ramakrishnan D, Avesta A, de Oliveira Santo I, Jin L, Huttner A, Bousabarah K, Ikuta I, Lin M, Aneja S, Turowski B, Aboian M, Moliterno J. Application of novel PACS-based informatics platform to identify imaging based predictors of CDKN2A allelic status in glioblastomas. Scientific Reports 2023, 13: 22942. PMID: 38135704, PMCID: PMC10746716, DOI: 10.1038/s41598-023-48918-4.Peer-Reviewed Original ResearchConceptsInformatics platformDeep learning algorithmsImaging featuresCDKN2A alterationsLearning algorithmHeterozygous lossHomozygous deletionLarge datasetsDeep white matter invasionGBM molecular subtypesNew informaticsQualitative imaging biomarkersWhole-exome sequencingQualitative imaging featuresGBM resectionRadiographic evidenceWorse prognosisPACSMolecular subtypesPial invasionImaging biomarkersCDKN2A mutationsAllele statusNoninvasive identificationMagnetic resonance imagesThrombocyte-derived Dickkopf1 promotes macrophage polarization in the Bleomycin-induced lung injury model
Sung E, Park M, Song S, Alanya H, Henegariu O, Liu J, Erson-Omay E, Sime P, Chae W. Thrombocyte-derived Dickkopf1 promotes macrophage polarization in the Bleomycin-induced lung injury model. Frontiers In Immunology 2023, 14: 1247330. PMID: 38162655, PMCID: PMC10757334, DOI: 10.3389/fimmu.2023.1247330.Peer-Reviewed Original ResearchConceptsLung injury modelMacrophage polarizationTissue repair processInjury modelMonocyte-derived alveolar macrophagesInjury-induced inflammationTissue repairRepair processRole of WntGene expression profilesImmunomodulatory roleIL-13Tissue injuryImmune responseInflammationCollagen depositionAlveolar macrophagesMacrophagesTissue homeostasisProtein expressionGene expressionRegulatory ligandsExpression profilesWnt antagonist Dickkopf1Dickkopf1Mutation 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 ResearchSporadic pituitary adenoma with somatic double-hit loss of MEN1
Hong C, Alanya H, DiStasio M, Boulware S, Rimmer R, Omay S, Erson-Omay E. Sporadic pituitary adenoma with somatic double-hit loss of MEN1. Pituitary 2023, 26: 488-494. PMID: 37438451, DOI: 10.1007/s11102-023-01336-1.Peer-Reviewed Original ResearchContribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy
Khoshkhoo S, Wang Y, Chahine Y, Erson-Omay E, Robert S, Kiziltug E, Damisah E, Nelson-Williams C, Zhu G, Kong W, Huang A, Stronge E, Phillips H, Chhouk B, Bizzotto S, Chen M, Adikari T, Ye Z, Witkowski T, Lai D, Lee N, Lokan J, Scheffer I, Berkovic S, Haider S, Hildebrand M, Yang E, Gunel M, Lifton R, Richardson R, Blümcke I, Alexandrescu S, Huttner A, Heinzen E, Zhu J, Poduri A, DeLanerolle N, Spencer D, Lee E, Walsh C, Kahle K. Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy. JAMA Neurology 2023, 80: 578-587. PMID: 37126322, PMCID: PMC10152377, DOI: 10.1001/jamaneurol.2023.0473.Peer-Reviewed Original ResearchConceptsDrug-resistant mesial temporal lobe epilepsyMesial temporal lobe epilepsyPathogenic somatic variantsTemporal lobe epilepsyMedian ageLobe epilepsyTemporal neocortexHippocampal tissueLevel 4 epilepsy centerAvailable frozen tissueSomatic variantsControl brain tissueMedial temporal lobectomyNew therapeutic targetsMolecular assaysGene panel sequencingRas/Raf/MAPK signalingAntiseizure medicationsMost patientsCommon indicationGermline genetic variantsEpilepsy centersTemporal lobectomyEpilepsy surgerySex-matched neurotypical controlsClinical and genomic differences in supratentorial versus infratentorial NF2 mutant meningiomas.
Tabor J, O'Brien J, Vasandani S, Vetsa S, Lei H, Jalal M, Marianayagam N, Jin L, Millares Chavez M, Haynes J, Dincer A, Yalcin K, Aguilera S, Omay S, Mishra-Gorur K, McGuone D, Morales-Valero S, Fulbright R, Gunel M, Erson-Omay E, Moliterno J. Clinical and genomic differences in supratentorial versus infratentorial NF2 mutant meningiomas. Journal Of Neurosurgery 2023, 139: 1648-1656. PMID: 37243548, DOI: 10.3171/2023.4.jns222929.Peer-Reviewed Original ResearchConceptsSubtotal resectionSupratentorial tumorsElevated Ki-67High-risk featuresProgression-free survivalChromosome 1p deletionInfratentorial counterpartsInfratentorial tumorsPostoperative managementSomatic driver mutationsCerebral convexityGrade IIInfratentorial meningiomasKi-67Posterior fossaLoss of heterozygosityMeningiomasResectionTumorsWhole-exome sequencing dataDriver mutationsHigh gradeSignificant differencesExome sequencing dataSporadic meningiomasVascular steal and associated intratumoral aneurysms in highly vascular brain tumors: illustrative case
Hong C, Marianayagam N, Morales-Valero S, Barak T, Tabor J, O’Brien J, Huttner A, Baehring J, Gunel M, Erson-Omay E, Fulbright R, Matouk C, Moliterno J. Vascular steal and associated intratumoral aneurysms in highly vascular brain tumors: illustrative case. Journal Of Neurosurgery Case Lessons 2023, 5: case22512. PMID: 36880509, PMCID: PMC10550659, DOI: 10.3171/case22512.Peer-Reviewed Original ResearchVascular brain tumorsVascular stealIntratumoral aneurysmBrain tumorsAdditional vascular imagingRight ophthalmic arteryMaximal safe resectionDiagnostic cerebral angiographyMinimal blood lossVascular steal phenomenonOpen tumor resectionDural-based lesionsSteal phenomenonBlood lossCerebral angiographyClinical suspicionNeurological symptomsOphthalmic arterySurgical strategySafe resectionVascular tumorsBlurred visionEndovascular embolizationTomography angiographyTumor resectionEpstein-Barr virus–associated primary intracranial leiomyosarcoma in an immunocompetent patient: illustrative case
Tabor J, Lei H, Morales-Valero S, O’Brien J, Gopal P, Erson-Omay E, Fulbright R, Moliterno J. Epstein-Barr virus–associated primary intracranial leiomyosarcoma in an immunocompetent patient: illustrative case. Journal Of Neurosurgery Case Lessons 2023, 5: case22532. PMID: 36692065, PMCID: PMC10550697, DOI: 10.3171/case22532.Peer-Reviewed Original ResearchEpstein-Barr virusPrimary intracranial leiomyosarcomaHuman immunodeficiency virusImmunocompetent statusImmunocompetent patientsIntracranial leiomyosarcomaMainstay of treatmentGross total resectionLeft-sided headacheSmooth muscle tumorsLeft middle cranial fossaMagnetic resonance imagingMiddle cranial fossaDura-based massUncomplicated resectionPrompt diagnosisTotal resectionAssociated edemaImmunodeficiency virusPoor prognosisMuscle tumorsRare diagnosisRare tumorImmunocompromised individualsPatients
2022
Spectrum of qualitative and quantitative imaging of pilomyxoid, intermediate pilomyxoid and pilocytic astrocytomas in relation to their genetic alterations
Fadel SA, von Reppert M, Kazarian E, Omay EZE, Marks A, Linder N, Hoffmann KT, Darbinyan A, Huttner A, Aboian MS. Spectrum of qualitative and quantitative imaging of pilomyxoid, intermediate pilomyxoid and pilocytic astrocytomas in relation to their genetic alterations. Neuroradiology 2022, 65: 195-205. PMID: 35984480, DOI: 10.1007/s00234-022-03027-3.Peer-Reviewed Original ResearchConceptsPilocytic astrocytomaImaging characteristicsADC valuesAggressive imaging characteristicsSuprasellar pilocytic astrocytomaRecurrence/progressionPediatric brain tumorsFrontal white matterWhole-exome sequencingPilomyxoid astrocytomaIntraventricular extensionSuprasellar regionThird ventriclePosterior fossaAtypical locationBrain tumorsWhite matterGrade 1TumorsAstrocytomasDriver mutationsExome sequencingGenetic alterationsPatientsHippocampusBiallelic inactivation of PBRM1 as a molecular driver in a rare pineoblastoma case: illustrative case
Antonios JP, Yalcin K, Darbinyan A, Koo A, Hong CS, DiLuna M, Erson-Omay Z. Biallelic inactivation of PBRM1 as a molecular driver in a rare pineoblastoma case: illustrative case. Journal Of Neurosurgery Case Lessons 2022, 3: case2213. PMID: 36303510, PMCID: PMC9379698, DOI: 10.3171/case2213.Peer-Reviewed Original ResearchMolecular driversPineal parenchymal tumorsRenal cell carcinomaRare tumor typeParenchymal tumorsCell carcinomaBladder carcinomaPapillary featuresPineoblastomaTumor subtypesTumor typesConsensus groupBiallelic lossGenomic profilingCancer typesMolecular level alterationsLevel alterationsGenomic driversBiallelic inactivationCarcinomaDriver eventsTumor suppressorGenetic phenotypesPathway changesMultiomics studies
2021
PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans
Barak T, Ristori E, Ercan-Sencicek AG, Miyagishima DF, Nelson-Williams C, Dong W, Jin SC, Prendergast A, Armero W, Henegariu O, Erson-Omay EZ, Harmancı AS, Guy M, Gültekin B, Kilic D, Rai DK, Goc N, Aguilera SM, Gülez B, Altinok S, Ozcan K, Yarman Y, Coskun S, Sempou E, Deniz E, Hintzen J, Cox A, Fomchenko E, Jung SW, Ozturk AK, Louvi A, Bilgüvar K, Connolly ES, Khokha MK, Kahle KT, Yasuno K, Lifton RP, Mishra-Gorur K, Nicoli S, Günel M. PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans. Nature Medicine 2021, 27: 2165-2175. PMID: 34887573, PMCID: PMC8768030, DOI: 10.1038/s41591-021-01572-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesPeptidyl-prolyl cis-transPathogenesis of IAContribution of variantsCommon genetic variantsVertebrate modelDeleterious mutationsWnt activatorAssociation studiesWhole-exome sequencingSignificant enrichmentGenetic variantsWntAngiogenesis regulatorsMutationsGene mutationsBrain angiogenesisIntracranial aneurysm ruptureJMJD6AngiogenesisCerebrovascular morphologyCerebrovascular integrityIntracerebral hemorrhageAneurysm ruptureVariantsComprehensive Genomic Characterization of A Case of Granular Cell Tumor of the Posterior Pituitary Gland: A Case Report
Hong CS, Elsamadicy AA, Fisayo A, Inzucchi SE, Gopal PP, Vining EM, Erson-Omay EZ, Omay S. Comprehensive Genomic Characterization of A Case of Granular Cell Tumor of the Posterior Pituitary Gland: A Case Report. Frontiers In Endocrinology 2021, 12: 762095. PMID: 34925233, PMCID: PMC8671743, DOI: 10.3389/fendo.2021.762095.Peer-Reviewed Original ResearchConceptsGranular cell tumorPosterior pituitary glandCell tumorsPituitary glandComprehensive genomic characterizationWhole-exome sequencingImmune checkpoint inhibitorsPoor clinical outcomePituitary gland tumorsHistone deacetylase inhibitorsInstitutional review boardRadiographic compressionUnderwent resectionCheckpoint inhibitorsMedical therapyPituitary massClinical outcomesOptic nerveSignificant morbidityResidual diseaseCase reportCentral hypothyroidismPharmacologic agentsGland tumorsTherapeutic targeting