Featured Publications
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 growthSingle-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 gliomas
2024
A brave new framework for glioma drug development
Hotchkiss K, Karschnia P, Schreck K, Geurts M, Cloughesy T, Huse J, Duke E, Lathia J, Ashley D, Nduom E, Long G, Singh K, Chalmers A, Ahluwalia M, Heimberger A, Bagley S, Todo T, Verhaak R, Kelly P, Hervey-Jumper S, de Groot J, Patel A, Fecci P, Parney I, Wykes V, Watts C, Burns T, Sanai N, Preusser M, Tonn J, Drummond K, Platten M, Das S, Tanner K, Vogelbaum M, Weller M, Whittle J, Berger M, Khasraw M. A brave new framework for glioma drug development. The Lancet Oncology 2024, 25: e512-e519. PMID: 39362262, DOI: 10.1016/s1470-2045(24)00190-6.Peer-Reviewed Original ResearchConceptsBrain tumorsBenefits of biopsyBrain tumor therapyLiquid biopsy technologiesTissue samplesPostoperative deficitsBiopsy techniqueBiopsy technologyEffective therapySurgical trialsClinical trialsTumor therapyResistance mechanismsTumorTherapyPatientsDrug developmentTissue analysisBrainTrialsTissueBiopsyGliomaRegulatory agencies
2023
[18F]-fluoroethyl-L-tyrosine (FET) in glioblastoma (FIG) TROG 18.06 study: protocol for a prospective, multicentre PET/CT trial
Koh E, Gan H, Senko C, Francis R, Ebert M, Lee S, Lau E, Khasraw M, Nowak A, Bailey D, Moffat B, Fitt G, Hicks R, Coffey R, Verhaak R, Walsh K, Barnes E, De Abreu Lourenco R, Rosenthal M, Adda L, Foroudi F, Lasocki A, Moore A, Thomas P, Roach P, Back M, Leonard R, Scott A. [18F]-fluoroethyl-L-tyrosine (FET) in glioblastoma (FIG) TROG 18.06 study: protocol for a prospective, multicentre PET/CT trial. BMJ Open 2023, 13: e071327. PMID: 37541751, PMCID: PMC10407346, DOI: 10.1136/bmjopen-2022-071327.Peer-Reviewed Original ResearchConceptsFET PETPositron emission tomographyPrimary central nervous system cancerTumor progressionCentral nervous system cancerL-tyrosine positron emission tomographyFET-PET imagingPhase II studyCo-primary outcomesProgression-free survivalMaximal safe resectionPost-chemotherapy treatmentNervous system cancersHealth economic impactHuman Research Ethics CommitteePatterns of failureTrue tumor progressionGood clinical practiceDeclaration of HelsinkiRadiological progressionConcurrent chemoradiationInitial surgeryPostoperative radiotherapyII studyOverall survivalCorrecting the drug development paradigm for glioblastoma requires serial tissue sampling
Singh K, Hotchkiss K, Parney I, De Groot J, Sahebjam S, Sanai N, Platten M, Galanis E, Lim M, Wen P, Minniti G, Colman H, Cloughesy T, Mehta M, Geurts M, Arrillaga-Romany I, Desjardins A, Tanner K, Short S, Arons D, Duke E, Wick W, Bagley S, Ashley D, Kumthekar P, Verhaak R, Chalmers A, Patel A, Watts C, Fecci P, Batchelor T, Weller M, Vogelbaum M, Preusser M, Berger M, Khasraw M. Correcting the drug development paradigm for glioblastoma requires serial tissue sampling. Nature Medicine 2023, 29: 2402-2405. PMID: 37488293, DOI: 10.1038/s41591-023-02464-8.Peer-Reviewed Original ResearchHemizygous CDKN2A deletion confers worse survival outcomes in IDHmut-noncodel gliomas
Kocakavuk E, Johnson K, Sabedot T, Reinhardt H, Noushmehr H, Verhaak R. Hemizygous CDKN2A deletion confers worse survival outcomes in IDHmut-noncodel gliomas. Neuro-Oncology 2023, 25: 1721-1723. PMID: 37329568, PMCID: PMC10479907, DOI: 10.1093/neuonc/noad095.Peer-Reviewed Original Research
2021
Spatial 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
2020
Comparative Molecular Life History of Spontaneous Canine and Human Gliomas
Amin S, Anderson K, Boudreau C, Martinez-Ledesma E, Kocakavuk E, Johnson K, Barthel F, Varn F, Kassab C, Ling X, Kim H, Barter M, Lau C, Ngan C, Chapman M, Koehler J, Long J, Miller A, Miller C, Porter B, Rissi D, Mazcko C, LeBlanc A, Dickinson P, Packer R, Taylor A, Rossmeisl J, Woolard K, Heimberger A, Levine J, Verhaak R. Comparative Molecular Life History of Spontaneous Canine and Human Gliomas. Cancer Cell 2020, 37: 243-257.e7. PMID: 32049048, PMCID: PMC7132629, DOI: 10.1016/j.ccell.2020.01.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsDNA MethylationDogsExomeGliomaHumansIsocitrate DehydrogenaseMutationTumor Suppressor Protein p53ConceptsComparative genomic analysisDNA methylation patternsReceptor tyrosine kinasesCell cycle pathwayGenomic analysisMethylation sequencingLife historyMutational processesTyrosine kinaseHigh similarityHuman gliomasTumorigenic mechanismsHost environmentMutational rateSomatic alterationsSporadic gliomasIDH1 R132Canine gliomasMolecular profileGlioma etiologyHuman pediatricPediatric gliomasTranscriptomeKinaseUnique insights
2018
Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma
deCarvalho A, Kim H, Poisson L, Winn M, Mueller C, Cherba D, Koeman J, Seth S, Protopopov A, Felicella M, Zheng S, Multani A, Jiang Y, Zhang J, Nam D, Petricoin E, Chin L, Mikkelsen T, Verhaak R. Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma. Nature Genetics 2018, 50: 708-717. PMID: 29686388, PMCID: PMC5934307, DOI: 10.1038/s41588-018-0105-0.Peer-Reviewed Original ResearchConceptsExtrachromosomal DNA elementsDNA elementsChromosomal DNA alterationsDNA alterationsSomatic driver alterationsGenomic heterogeneitySingle nucleotide variantsOffspring cellsDiscordant inheritanceExtrachromosomal elementsEcDNAsGBM evolutionOncogenic potentialGBM samplesInheritance patternChromosomal alterationsSelection dynamicsModel systemCell culturesOrthotopic xenograft modelDriver alterationsXenograft modelOncogene amplificationCellsGlioblastoma
2012
Studying a Complex Tumor
Zheng S, Chheda M, Verhaak R. Studying a Complex Tumor. The Cancer Journal 2012, 18: 107-114. PMID: 22290264, PMCID: PMC3342695, DOI: 10.1097/ppo.0b013e3182431c57.Peer-Reviewed Original ResearchConceptsGenomic alterationsRecurrent genomic alterationsDNA copy numberGenomic studiesGenomic researchCopy numberExpression signaturesGenomic abnormalitiesGlioblastoma multiforme samplesExpression subtypesNew insightsGenesGlioblastoma multiformeGlioblastoma multiforme therapyHeterogeneous diseaseHigh specificityAlterationsTP53IDH1Identification