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 growthLive-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer
Yi E, Gujar A, Guthrie M, Kim H, Zhao D, Johnson K, Amin S, Costa M, Yu Q, Das S, Jillette N, Clow P, Cheng A, Verhaak R. Live-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer. Cancer Discovery 2022, 12: 468-483. PMID: 34819316, PMCID: PMC8831456, DOI: 10.1158/2159-8290.cd-21-1376.Peer-Reviewed Original ResearchConceptsExtrachromosomal DNA elementsDNA elementsUneven segregationRNA polymerase IILive-cell imagingPolymerase IIOffspring cellsGene transcriptionCell line modelsEcDNAsRandom segregationGenetic materialLiving cellsCopy numberLive cellsIndividual cellsTumor evolutionMitosisInheritance patternBreakpoint sequencesIssue featureTranscriptionFluorescent markersPatient tissuesCells
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 ResearchRadiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer
Kocakavuk E, Anderson K, Varn F, Johnson K, Amin S, Sulman E, Lolkema M, Barthel F, Verhaak R. Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer. Nature Genetics 2021, 53: 1088-1096. PMID: 34045764, PMCID: PMC8483261, DOI: 10.1038/s41588-021-00874-3.Peer-Reviewed Original ResearchConceptsWorse clinical outcomesNon-irradiated tumorsClinical outcomesRecurrent cancerPatient survivalPoor outcomeMetastatic tumorsRecurrent gliomaRadiation therapyRadiation-induced DNA damageDNA damageGlioma Longitudinal Analysis ConsortiumMutational signature analysisCancer treatmentDeletion burdenRadiotherapyMedical FoundationAPOBEC mutagenesisSignificant increaseTumorsCancerDNA damage repairDeletion signatureMutational spectrumSmall deletions
2020
Molecular and clonal evolution in recurrent metastatic gliosarcoma
Anderson K, Tan A, Parkinson J, Back M, Kastelan M, Newey A, Brewer J, Wheeler H, Hudson A, Amin S, Johnson K, Barthel F, Verhaak R, Khasraw M. Molecular and clonal evolution in recurrent metastatic gliosarcoma. Molecular Case Studies 2020, 6: a004671. PMID: 31896544, PMCID: PMC6996521, DOI: 10.1101/mcs.a004671.Peer-Reviewed Original ResearchConceptsFirst recurrenceExtracranial metastasesIntracranial tumorsFrontal lobeRight iliac boneLeft frontal lobeOrigin of metastasesFrontal recurrenceMetastatic gliosarcomaConcurrent radiotherapyFurther surgeryFurther recurrenceRecurrent tumorsMetastatic tumorsIliac boneMetastasisRecurrenceTumorsMesenchymal typeSurgeryClonal relationshipRadiotherapyGliosarcomaMolecular profilePelvic bones
2019
Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue
Wilkins O, Johnson K, Houseman E, King J, Marsit C, Christensen B. Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue. Epigenetics 2019, 15: 398-418. PMID: 31842685, PMCID: PMC7153548, DOI: 10.1080/15592294.2019.1695332.Peer-Reviewed Original ResearchConceptsGenome-wide characterizationGenome-wide patternsGenome-wide mapsGene regulatory programsActive chromatinGenomic lociGene regulationTranscriptional inactivityRegulatory regionsGene regionMammalian tissuesRegulatory programsCpG lociDNA treatmentImmune cell functionCell functionLociLactate oxidationNormal breast tissueIndependent data setsPre-invasive breast cancerRecent evidenceHeterochromatinChromatinBisulfiteBMP 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 functionGenesDNARegulationAnnotationOxyBS: estimation of 5-methylcytosine and 5-hydroxymethylcytosine from tandem-treated oxidative bisulfite and bisulfite DNA
Houseman E, Johnson K, Christensen B. OxyBS: estimation of 5-methylcytosine and 5-hydroxymethylcytosine from tandem-treated oxidative bisulfite and bisulfite DNA. Bioinformatics 2016, 32: 2505-2507. PMID: 27153596, PMCID: PMC4978924, DOI: 10.1093/bioinformatics/btw158.Peer-Reviewed Original Research
2014
Genome-wide DNA methylation profiles in progression to in situand invasive carcinoma of the breast with impact on gene transcription and prognosis
Fleischer T, Frigessi A, Johnson K, Edvardsen H, Touleimat N, Klajic J, Riis M, Haakensen V, Wärnberg F, Naume B, Helland Å, Børresen-Dale A, Tost J, Christensen B, Kristensen V. Genome-wide DNA methylation profiles in progression to in situand invasive carcinoma of the breast with impact on gene transcription and prognosis. Genome Biology 2014, 15: 435. PMID: 25146004, PMCID: PMC4165906, DOI: 10.1186/s13059-014-0435-x.Peer-Reviewed Original ResearchConceptsGenome-wide DNA methylation profilesDNA methylation profilesMethylation profilesInvasive breast carcinomaProgression of cancerBreast carcinomaDNA methylation alterationsPrognostic signatureDNA methylation-based markersCancer Genome AtlasDNA methylationGene transcriptionMethylation changesMethylation-based markersEpigenetic changesMethylation alterationsSurvival of patientsGene expressionBreast cancer patientsMethylation levelsNormal breast tissueBreast cancer samplesClinical decision makingGenesGenome Atlas
2013
Age-related DNA methylation in normal breast tissue and its relationship with invasive breast tumor methylation
Johnson K, Koestler D, Cheng C, Christensen B. Age-related DNA methylation in normal breast tissue and its relationship with invasive breast tumor methylation. Epigenetics 2013, 9: 268-275. PMID: 24196486, PMCID: PMC3962537, DOI: 10.4161/epi.27015.Peer-Reviewed Original Research