2021
Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy
Terranova C, Tang M, Maitituoheti M, Raman A, Ghosh A, Schulz J, Amin S, Orouji E, Tomczak K, Sarkar S, Oba J, Creasy C, Wu C, Khan S, Lazcano R, Wani K, Singh A, Barrodia P, Zhao D, Chen K, Haydu L, Wang W, Lazar A, Woodman S, Bernatchez C, Rai K. Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy. Cell Reports 2021, 36: 109410. PMID: 34289358, PMCID: PMC8369408, DOI: 10.1016/j.celrep.2021.109410.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationChromatinEnhancer of Zeste Homolog 2 ProteinFemaleGTP PhosphohydrolasesHistonesHumansMelanocytesMelanomaMembrane ProteinsMesodermMice, NudeMitogen-Activated Protein Kinase KinasesMutationNeoplasm MetastasisPolycomb Repressive Complex 2Transcription, GeneticTumor BurdenConceptsHistone H3 lysine 27 trimethylationH3 lysine 27 trimethylationBivalent chromatin stateCell identity genesLysine 27 trimethylationKey epigenetic alterationsNRAS mutantsMaster transcription factorBivalent domainsChromatin statePRC2 inhibitionEpigenetic elementsTranscription factorsEpigenetic alterationsGenetic driversMesenchymal phenotypeNRAS-mutant melanomaState profilingTherapeutic vulnerabilitiesInvasive capacityPharmacological inhibitionMutantsTherapeutic strategiesMelanoma samplesMutant melanoma patients
2020
KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer
Alam H, Tang M, Maitituoheti M, Dhar S, Kumar M, Han C, Ambati C, Amin S, Gu B, Chen T, Lin Y, Chen J, Muller F, Putluri N, Flores E, DeMayo F, Baseler L, Rai K, Lee M. KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. Cancer Cell 2020, 37: 599-617.e7. PMID: 32243837, PMCID: PMC7178078, DOI: 10.1016/j.ccell.2020.03.005.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAnimalsAntimetabolitesApoptosisBiomarkers, TumorCell ProliferationDeoxyglucoseDNA-Binding ProteinsEnhancer Elements, GeneticGene Expression Regulation, NeoplasticGlycolysisHistone-Lysine N-MethyltransferaseHistonesHumansLung NeoplasmsMiceMice, KnockoutMice, NudeMutationMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsPeriod Circadian ProteinsPrognosisTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsLung cancerLung-specific lossHuman lung cancer cellsExpression of Per2Lung cancer cellsHistone methyltransferase KMT2DLung tumor suppressorTumor suppressive roleMultiple glycolytic genesLung tumorigenesisEpigenetic modifiersPharmacological inhibitionTherapeutic vulnerabilitiesGlycolytic inhibitorCancerCancer cellsKMT2DFunction mutationsTumor suppressorPer2GlycolysisGlycolytic genesMutationsMice
2017
Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression
Fiziev P, Akdemir K, Miller J, Keung E, Samant N, Sharma S, Natale C, Terranova C, Maitituoheti M, Amin S, Martinez-Ledesma E, Dhamdhere M, Axelrad J, Shah A, Cheng C, Mahadeshwar H, Seth S, Barton M, Protopopov A, Tsai K, Davies M, Garcia B, Amit I, Chin L, Ernst J, Rai K. Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression. Cell Reports 2017, 19: 875-889. PMID: 28445736, PMCID: PMC5473172, DOI: 10.1016/j.celrep.2017.03.078.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationCell LineCell ProliferationChromatinChromatin ImmunoprecipitationDisease-Free SurvivalEpigenomicsHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHumansHydroxamic AcidsKaplan-Meier EstimateMelanomaPrincipal Component AnalysisPTEN PhosphohydrolaseRNA InterferenceRNA, Small InterferingSignal TransductionVorinostatConceptsChromatin state transitionsMelanoma progressionChromatin state changesGene expression patternsCancer regulatory genesChromatin stateEpigenomic profilingEpigenomic changesEpigenomic analysisTumorigenic stateEpigenetic modificationsTranscriptomic analysisRegulatory regionsHistone acetylationAcetylation changesHistone deacetylase inhibitorsExpression patternsHyperproliferative phenotypeAcetylation levelsTumorigenic cellsHuman melanoma cellsFunctional rolePhenotypic modelDeacetylase inhibitorsMelanoma cells