2022
Glioma progression is shaped by genetic evolution and microenvironment interactions
Varn F, Johnson K, Martinek J, Huse J, Nasrallah M, Wesseling P, Cooper L, Malta T, Wade T, Sabedot T, Brat D, Gould P, Wöehrer A, Aldape K, Ismail A, Sivajothi S, Barthel F, Kim H, Kocakavuk E, Ahmed N, White K, Datta I, Moon H, Pollock S, Goldfarb C, Lee G, Garofano L, Anderson K, Nehar-Belaid D, Barnholtz-Sloan J, Bakas S, Byrne A, D’Angelo F, Gan H, Khasraw M, Migliozzi S, Ormond D, Paek S, Van Meir E, Walenkamp A, Watts C, Weiss T, Weller M, Palucka K, Stead L, Poisson L, Noushmehr H, Iavarone A, Verhaak R, Consortium T, Varn F, Johnson K, Martinek J, Huse J, Nasrallah M, Wesseling P, Cooper L, Malta T, Wade T, Sabedot T, Brat D, Gould P, Wöehrer A, Aldape K, Ismail A, Sivajothi S, Barthel F, Kim H, Kocakavuk E, Ahmed N, White K, Datta I, Moon H, Pollock S, Goldfarb C, Lee G, Garofano L, Anderson K, Nehar-Belaid D, Barnholtz-Sloan J, Bakas S, Byrne A, D’Angelo F, Gan H, Khasraw M, Migliozzi S, Ormond D, Paek S, Van Meir E, Walenkamp A, Watts C, Weiss T, Weller M, Alfaro K, Amin S, Ashley D, Bock C, Brodbelt A, Bulsara K, Castro A, Connelly J, Costello J, de Groot J, Finocchiaro G, French P, Golebiewska A, Hau A, Hong C, Horbinski C, Kannan K, Kouwenhoven M, Lasorella A, LaViolette P, Ligon K, Lowman A, Mehta S, Miletic H, Molinaro A, Ng H, Niclou S, Niers J, Phillips J, Rabadan R, Rao G, Reifenberger G, Sanai N, Short S, Smitt P, Sloan A, Smits M, Snyder J, Suzuki H, Tabatabai G, Tanner G, Tomaszewski W, Wells M, Westerman B, Wheeler H, Xie J, Yung W, Zadeh G, Zhao J, Palucka K, Stead L, Poisson L, Noushmehr H, Iavarone A, Verhaak R. Glioma progression is shaped by genetic evolution and microenvironment interactions. Cell 2022, 185: 2184-2199.e16. PMID: 35649412, PMCID: PMC9189056, DOI: 10.1016/j.cell.2022.04.038.Peer-Reviewed Original ResearchConceptsSpecific ligand-receptor interactionsMicroenvironment interactionsDNA sequencing dataGlioma progressionLigand-receptor interactionsNeoplastic cellsSignaling programsCell statesSequencing dataGenetic evolutionGenetic changesIDH wild-type tumorsIsocitrate dehydrogenaseMesenchymal transitionSomatic alterationsDistinct mannerActive tumor growthIDH-mutant gliomasPotential targetTherapy resistanceAdult patientsDisease progressionPossible roleCellsTumor growth
2021
Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response
Johnson K, Anderson K, Courtois E, Gujar A, Barthel F, Varn F, Luo D, Seignon M, Yi E, Kim H, Estecio M, Zhao D, Tang M, Navin N, Maurya R, Ngan C, Verburg N, de Witt Hamer P, Bulsara K, Samuels M, Das S, Robson P, Verhaak R. Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response. Nature Genetics 2021, 53: 1456-1468. PMID: 34594038, PMCID: PMC8570135, DOI: 10.1038/s41588-021-00926-8.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsCell PlasticityClonal EvolutionDNA Copy Number VariationsDNA MethylationEpigenesis, GeneticGene Expression Regulation, NeoplasticGenetic HeterogeneityGenome, HumanGliomaHumansMutationPhylogenyPromoter Regions, GeneticSingle-Cell AnalysisStress, PhysiologicalTumor MicroenvironmentConceptsDNA methylation disorderEnvironmental stress responsesMethylation disordersEnvironmental stress response pathwaysStress responseStress response processesStress response pathwaysSingle-cell transcriptomesDNA methylation changesDNA methylation differencesDNA methylation dataMulti-omics profilesDNA methylomeTranscriptional disruptionEpigenetic instabilityEpigenetic heterogeneityEpigenetic regulatorsResponse pathwaysCellular plasticityMethylation changesMethylation differencesCell statesMethylation dataIrradiation stressWild-type gliomasSerum cell-free DNA epigenetic biomarkers aid glioma diagnostics and monitoring
Johnson K, Verhaak R. Serum cell-free DNA epigenetic biomarkers aid glioma diagnostics and monitoring. Neuro-Oncology 2021, 23: 1423-1424. PMID: 34139018, PMCID: PMC8408867, DOI: 10.1093/neuonc/noab146.Peer-Reviewed Original ResearchSpatial concordance of DNA methylation classification in diffuse glioma
Verburg N, Barthel F, Anderson K, Johnson K, Koopman T, Yaqub M, Hoekstra O, Lammertsma A, Barkhof F, Pouwels P, Reijneveld J, Rozemuller A, Beliën J, Boellaard R, Taylor M, Das S, Costello J, Vandertop W, Wesseling P, de Witt Hamer P, Verhaak R. Spatial concordance of DNA methylation classification in diffuse glioma. Neuro-Oncology 2021, 23: 2054-2065. PMID: 34049406, PMCID: PMC8643482, DOI: 10.1093/neuonc/noab134.Peer-Reviewed Original Research
2019
BMP signaling mediates glioma stem cell quiescence and confers treatment resistance in glioblastoma
Sachdeva R, Wu M, Johnson K, Kim H, Celebre A, Shahzad U, Graham M, Kessler J, Chuang J, Karamchandani J, Bredel M, Verhaak R, Das S. BMP signaling mediates glioma stem cell quiescence and confers treatment resistance in glioblastoma. Scientific Reports 2019, 9: 14569. PMID: 31602000, PMCID: PMC6787003, DOI: 10.1038/s41598-019-51270-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBone Morphogenetic Protein 4Bone Morphogenetic ProteinsBrain NeoplasmsCell DivisionCell Line, TumorCell ProliferationDisease ProgressionDrug Resistance, NeoplasmGlioblastomaGliomaHomeostasisHumansMiceMice, Inbred NODNeoplasm Recurrence, LocalNeoplasm TransplantationNeoplastic Stem CellsPhenotypeRNA, Small InterferingSequence Analysis, RNASignal TransductionTemozolomideTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsBMP pathway activationStem cell homeostasisStem cell systemStem cell quiescenceStem cell populationCancer stem cell populationInhibits cell proliferationStem-like cellsCancer stem cellsCell quiescenceCell homeostasisFunctional identityDismal prognosisTemozolomide chemotherapyCytotoxic therapyTumor recurrenceCellular reservoirsTreatment resistanceTherapeutic resistanceIncurable diseaseTumor progressionStem cellsCell proliferationPathway activationGlioblastoma
2018
Evolving Insights into the Molecular Neuropathology of Diffuse Gliomas in Adults
Barthel F, Johnson K, Wesseling P, Verhaak R. Evolving Insights into the Molecular Neuropathology of Diffuse Gliomas in Adults. Neurologic Clinics 2018, 36: 421-437. PMID: 30072063, PMCID: PMC6322909, DOI: 10.1016/j.ncl.2018.04.002.Peer-Reviewed Original ResearchConceptsDiffuse gliomasWorld Health Organization classificationAppropriate treatment regimensTreatment regimensOrganization classificationClinical classificationClinical relevanceMolecular neuropathologyPatient's lifeGliomasMolecular profilingMolecular biomarkersIntratumoral heterogeneityNeuropathologyAdultsOverview of studiesBiomarkersGene expressionMolecular analysisRegimensFacilitate selection
2016
5-Hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients
Johnson K, Houseman E, King J, von Herrmann K, Fadul C, Christensen B. 5-Hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients. Nature Communications 2016, 7: 13177. PMID: 27886174, PMCID: PMC5133638, DOI: 10.1038/ncomms13177.Peer-Reviewed Original ResearchMeSH Keywords5-MethylcytosineAdultAgedAged, 80 and overBrain NeoplasmsDNA MethylationDNA, NeoplasmEnhancer Elements, GeneticFemaleGene Expression Regulation, NeoplasticGene Regulatory NetworksGlioblastomaHumansIsocitrate DehydrogenaseMaleMiddle AgedPrefrontal CortexSurvival AnalysisTranscription FactorsConceptsRNA regulatory processesTissue-specific transcriptionDisease critical genesMethylation array dataGenomic distributionGenomic localizationCell maintenanceOxidative bisulfite (oxBS) treatmentTranscription factorsEnhancer elementsPrefrontal cortex tissueBisulfite treatmentCellular proliferationRegulatory processesTranscriptionArray dataMolecular alterationsCortex tissueEpigenomeGlioblastomaImmune functionGenesDNARegulationAnnotation