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 ResearchMeSH KeywordsAdultBrain NeoplasmsEvolution, MolecularGenes, p16GliomaHumansIsocitrate DehydrogenaseMutationNeoplasm Recurrence, LocalTumor MicroenvironmentConceptsSpecific 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
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 ResearchMeSH KeywordsDNA DamageHumansMutagenesisNeoplasm Recurrence, LocalNeoplasmsPrognosisRadiation, IonizingRadiotherapySequence DeletionConceptsWorse 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
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