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
2020
Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers
Kim H, Nguyen N, Turner K, Wu S, Gujar A, Luebeck J, Liu J, Deshpande V, Rajkumar U, Namburi S, Amin S, Yi E, Menghi F, Schulte J, Henssen A, Chang H, Beck C, Mischel P, Bafna V, Verhaak R. Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Nature Genetics 2020, 52: 891-897. PMID: 32807987, PMCID: PMC7484012, DOI: 10.1038/s41588-020-0678-2.Peer-Reviewed Original ResearchConceptsOncogene amplificationPoor outcomeCancer typesEcDNA amplificationShorter survivalCancer patientsMost cancer typesExtrachromosomal DNA amplificationsClinical impactMultiple cancersPatientsNormal tissuesCancerTranscript fusionsEnhanced chromatin accessibilityIntratumoral genetic heterogeneityOncogene transcriptionChromosomal amplificationOutcomesGenetic heterogeneityHigh levelsDNA amplificationTissue typesBloodComparative 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 ResearchConceptsComparative 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
2019
Longitudinal molecular trajectories of diffuse glioma in adults
Barthel FP, Johnson KC, Varn FS, Moskalik AD, Tanner G, Kocakavuk E, Anderson KJ, Abiola O, Aldape K, Alfaro KD, Alpar D, Amin SB, Ashley DM, Bandopadhayay P, Barnholtz-Sloan JS, Beroukhim R, Bock C, Brastianos PK, Brat DJ, Brodbelt AR, Bruns AF, Bulsara KR, Chakrabarty A, Chakravarti A, Chuang JH, Claus EB, Cochran EJ, Connelly J, Costello JF, Finocchiaro G, Fletcher MN, French PJ, Gan HK, Gilbert MR, Gould PV, Grimmer MR, Iavarone A, Ismail A, Jenkinson MD, Khasraw M, Kim H, Kouwenhoven MCM, LaViolette PS, Li M, Lichter P, Ligon KL, Lowman AK, Malta TM, Mazor T, McDonald KL, Molinaro AM, Nam DH, Nayyar N, Ng HK, Ngan CY, Niclou SP, Niers JM, Noushmehr H, Noorbakhsh J, Ormond DR, Park CK, Poisson LM, Rabadan R, Radlwimmer B, Rao G, Reifenberger G, Sa JK, Schuster M, Shaw BL, Short SC, Smitt PAS, Sloan AE, Smits M, Suzuki H, Tabatabai G, Van Meir EG, Watts C, Weller M, Wesseling P, Westerman BA, Widhalm G, Woehrer A, Yung WKA, Zadeh G, Huse JT, De Groot JF, Stead LF, Verhaak RGW. Longitudinal molecular trajectories of diffuse glioma in adults. Nature 2019, 576: 112-120. PMID: 31748746, PMCID: PMC6897368, DOI: 10.1038/s41586-019-1775-1.Peer-Reviewed Original ResearchConceptsAdult patientsDiffuse gliomasRecurrent gliomaOverall survivalPoor outcomeCurrent therapiesChromosome arms 1p/19qAcquired alterationsMajor subtypesTherapeutic resistanceGliomasGlioma developmentGene alterationsIDH mutationsGlioma subtypesPatientsHypermutator phenotypeDriver genesSubtypesClinical annotationSurvivalSubclonal selectionCell cycleAlterationsLittle evidence
2024
DNAR-16. TARGETING APOBEC CYTIDINE DEAMINASES TO ENHANCE RADIOSENSITIVITY IN GLIOMA
Marin B, Gujar A, Kocakavuk E, Johnson K, Amin S, Verhaak R. DNAR-16. TARGETING APOBEC CYTIDINE DEAMINASES TO ENHANCE RADIOSENSITIVITY IN GLIOMA. Neuro-Oncology 2024, 26: viii120-viii121. PMCID: PMC11553289, DOI: 10.1093/neuonc/noae165.0467.Peer-Reviewed Original ResearchApolipoprotein B mRNA-editing enzyme catalytic polypeptide-likeRadiation therapyNon-homologous end joiningRecurrent gliomaDNA-dependent protein kinaseMutational signaturesRT-induced DNA damageMonitoring response to treatmentRadiosensitivity in vitroEnhanced radiosensitivity in vitroA3GPromote tumor evolutionResponse to treatmentAutophosphorylation of DNA-dependent protein kinaseAPOBEC mutational signaturesAdult brain tumorsPrimary adult brain tumorGlioma Longitudinal Analysis ConsortiumFamily of cytidine deaminasesRadiosensitizing gliomasAPOBEC3G (A3GNon-homologous end-joining pathwayPost-RTGlioma cell linesWhole-genome sequencing
2021
Radiotherapy 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
2017
TumorFusions: an integrative resource for cancer-associated transcript fusions
Hu X, Wang Q, Tang M, Barthel F, Amin S, Yoshihara K, Lang F, Martinez-Ledesma E, Lee S, Zheng S, Verhaak R. TumorFusions: an integrative resource for cancer-associated transcript fusions. Nucleic Acids Research 2017, 46: gkx1018-. PMID: 29099951, PMCID: PMC5753333, DOI: 10.1093/nar/gkx1018.Peer-Reviewed Original ResearchConceptsTranscript fusionsGene fusionsWhole-genome sequencing dataSomatic DNA rearrangementsTranscript-level expressionGenome sequencing dataGene annotationCopy number levelsCancer samplesCancer Genome AtlasDNA rearrangementsUniform pipelineFunctional fusionSequencing dataIntegrative resourceLevel expressionPartner genesGenome AtlasChromosomal alterationsMutational patternsCancer typesFusion transcriptsNon-neoplastic samplesMolecular aberrationsNumber levels