PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma
Fons NR, Sundaram RK, Breuer GA, Peng S, McLean RL, Kalathil AN, Schmidt MS, Carvalho DM, Mackay A, Jones C, Carcaboso ÁM, Nazarian J, Berens ME, Brenner C, Bindra RS. PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma. Nature Communications 2019, 10: 3790. PMID: 31439867, PMCID: PMC6706443, DOI: 10.1038/s41467-019-11732-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBrain Stem NeoplasmsCell Line, TumorChildCytokinesDiffuse Intrinsic Pontine GliomaDNA MethylationEpigenetic RepressionFemaleGene Expression Regulation, NeoplasticHumansMiceNicotinamide PhosphoribosyltransferasePonsPrimary Cell CultureProtein Phosphatase 2CSynthetic Lethal MutationsXenograft Model Antitumor AssaysConceptsNicotinic acid phosphoribosyltransferaseSynthetic lethal interactionsNAMPT inhibitorsTumor-specific cell killingProtein phosphataseEpigenetic silencingMutant cellsKey genesCpG islandsLethal interactionsNAD biosynthesisGene expressionInhibitor sensitivityNAD metabolismOncogenic rolePediatric gliomasMutationsModel systemCell killingDriver mutationsPediatric high-grade gliomasMutant tumorsOncogenic driver mutationsNicotinamide phosphoribosyltransferase (NAMPT) inhibitionGenomeDNMT3A co-mutation in an IDH1-mutant glioblastoma
Fomchenko EI, Erson-Omay EZ, Zhao A, Bindra RS, Huttner A, Fulbright RK, Moliterno J. DNMT3A co-mutation in an IDH1-mutant glioblastoma. Molecular Case Studies 2019, 5: a004119. PMID: 31371348, PMCID: PMC6672028, DOI: 10.1101/mcs.a004119.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkers, TumorBrain NeoplasmsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ADNA Modification MethylasesEpigenesis, GeneticGene Expression ProfilingGene Expression Regulation, NeoplasticGlioblastomaGliomaHumansIsocitrate DehydrogenaseMaleMutationMutation, MissensePromoter Regions, GeneticConceptsIDH1-mutant glioblastomaEpigenetic controlHistone modificationsTranscriptional regulationDNA methylationExpression profilesGlioblastoma biologySomatic mutationsDe novoMutationsMutant glioblastomasTumor landscapeMutational profileTargeted therapeutic approachesGlioblastomaImportant roleMethylationDNMT3ABiologyGliomagenesisMissenseRegulationNovoPrimary brain tumorsTherapeutic approaches