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
Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma
Maitituoheti M, Keung E, Tang M, Yan L, Alam H, Han G, Singh A, Raman A, Terranova C, Sarkar S, Orouji E, Amin S, Sharma S, Williams M, Samant N, Dhamdhere M, Zheng N, Shah T, Shah A, Axelrad J, Anvar N, Lin Y, Jiang S, Chang E, Ingram D, Wang W, Lazar A, Lee M, Muller F, Wang L, Ying H, Rai K. Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma. Cell Reports 2020, 33: 108293. PMID: 33086062, PMCID: PMC7649750, DOI: 10.1016/j.celrep.2020.108293.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell Line, TumorDNA-Binding ProteinsFemaleGenes, Tumor SuppressorGlucoseGlycolysisHistone MethyltransferasesHistone-Lysine N-MethyltransferaseHumansInsulinIntercellular Signaling Peptides and ProteinsMaleMelanomaMiceMice, Inbred C57BLMice, NudeMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsReceptor, IGF Type 1Regulatory Sequences, Nucleic AcidSignal TransductionXenograft Model Antitumor AssaysConceptsKMT2D-deficient cellsInsulin growth factorEnhancer reprogrammingIGF1R-AktMelanocyte-specific deletionMutant melanomaMouse modelTumor typesTherapeutic interventionsPharmacological inhibitionPathway inhibitorPotent tumor suppressorIGF signalingGrowth factorMelanomaPooled RNAi screensSomatic point mutationsTumor suppressorKey metabolic pathwaysFrequent lossGlycolysisGlycolysis enzymesTumorigenesisGlycolysis pathwayMetabolic pathways
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
2015
Genomic Classification of Cutaneous Melanoma
Network T, Akbani R, Akdemir K, Aksoy B, Albert M, Ally A, Amin S, Arachchi H, Arora A, Auman J, Ayala B, Baboud J, Balasundaram M, Balu S, Barnabas N, Bartlett J, Bartlett P, Bastian B, Baylin S, Behera M, Belyaev D, Benz C, Bernard B, Beroukhim R, Bir N, Black A, Bodenheimer T, Boice L, Boland G, Bono R, Bootwalla M, Bosenberg M, Bowen J, Bowlby R, Bristow C, Brockway-Lunardi L, Brooks D, Brzezinski J, Bshara W, Buda E, Burns W, Butterfield Y, Button M, Calderone T, Cappellini G, Carter C, Carter S, Cherney L, Cherniack A, Chevalier A, Chin L, Cho J, Cho R, Choi Y, Chu A, Chudamani S, Cibulskis K, Ciriello G, Clarke A, Coons S, Cope L, Crain D, Curley E, Danilova L, D’Atri S, Davidsen T, Davies M, Delman K, Demchok J, Deng Q, Deribe Y, Dhalla N, Dhir R, DiCara D, Dinikin M, Dubina M, Ebrom J, Egea S, Eley G, Engel J, Eschbacher J, Fedosenko K, Felau I, Fennell T, Ferguson M, Fisher S, Flaherty K, Frazer S, Frick J, Fulidou V, Gabriel S, Gao J, Gardner J, Garraway L, Gastier-Foster J, Gaudioso C, Gehlenborg N, Genovese G, Gerken M, Gershenwald J, Getz G, Gomez-Fernandez C, Gribbin T, Grimsby J, Gross B, Guin R, Gutschner T, Hadjipanayis A, Halaban R, Hanf B, Haussler D, Haydu L, Hayes D, Hayward N, Heiman D, Herbert L, Herman J, Hersey P, Hoadley K, Hodis E, Holt R, Hoon D, Hoppough S, Hoyle A, Huang F, Huang M, Huang S, Hutter C, Ibbs M, Iype L, Jacobsen A, Jakrot V, Janning A, Jeck W, Jefferys S, Jensen M, Jones C, Jones S, Ju Z, Kakavand H, Kang H, Kefford R, Khuri F, Kim J, Kirkwood J, Klode J, Korkut A, Korski K, Krauthammer M, Kucherlapati R, Kwong L, Kycler W, Ladanyi M, Lai P, Laird P, Lander E, Lawrence M, Lazar A, Łaźniak R, Lee D, Lee J, Lee J, Lee K, Lee S, Lee W, Leporowska E, Leraas K, Li H, Lichtenberg T, Lichtenstein L, Lin P, Ling S, Liu J, Liu O, Liu W, Long G, Lu Y, Ma, Ma Y, Mackiewicz A, Mahadeshwar H, Malke J, Mallery D, Manikhas G, Mann G, Marra M, Matejka B, Mayo M, Mehrabi S, Meng S, Meyerson M, Mieczkowski P, Miller J, Miller M, Mills G, Moiseenko F, Moore R, Morris S, Morrison C, Morton D, Moschos S, Mose L, Muller F, Mungall A, Murawa D, Murawa P, Murray B, Nezi L, Ng S, Nicholson D, Noble M, Osunkoya A, Owonikoko T, Ozenberger B, Pagani E, Paklina O, Pantazi A, Parfenov M, Parfitt J, Park P, Park W, Parker J, Passarelli F, Penny R, Perou C, Pihl T, Potapova O, Prieto V, Protopopov A, Quinn M, Radenbaugh A, Rai K, Ramalingam S, Raman A, Ramirez N, Ramirez R, Rao U, Rathmell W, Ren X, Reynolds S, Roach J, Robertson A, Ross M, Roszik J, Russo G, Saksena G, Saller C, Samuels Y, Sander C, Sander C, Sandusky G, Santoso N, Saul M, Saw R, Schadendorf D, Schein J, Schultz N, Schumacher S, Schwallier C, Scolyer R, Seidman J, Sekhar P, Sekhon H, Senbabaoglu Y, Seth S, Shannon K, Sharpe S, Sharpless N, Shaw K, Shelton C, Shelton T, Shen R, Sheth M, Shi Y, Shiau C, Shmulevich I, Sica G, Simons J, Sinha R, Sipahimalani P, Sofia H, Soloway M, Song X, Sougnez C, Spillane A, Spychała A, Stretch J, Stuart J, Suchorska W, Sucker A, Sumer S, Sun Y, Synott M, Tabak B, Tabler T, Tam A, Tan D, Tang J, Tarnuzzer R, Tarvin K, Tatka H, Taylor B, Teresiak M, Thiessen N, Thompson J, Thorne L, Thorsson V, Trent J, Triche T, Tsai K, Tsou P, Van Den Berg D, Van Allen E, Veluvolu U, Verhaak R, Voet D, Voronina O, Walter V, Walton J, Wan Y, Wang Y, Wang Z, Waring S, Watson I, Weinhold N, Weinstein J, Weisenberger D, White P, Wilkerson M, Wilmott J, Wise L, Wiznerowicz M, Woodman S, Wu C, Wu C, Wu J, Wu Y, Xi R, Xu A, Yang D, Yang L, Yang L, Zack T, Zenklusen J, Zhang H, Zhang J, Zhang W, Zhao X, Zhu J, Zhu K, Zimmer L, Zmuda E, Zou L. Genomic Classification of Cutaneous Melanoma. Cell 2015, 161: 1681-1696. PMID: 26091043, PMCID: PMC4580370, DOI: 10.1016/j.cell.2015.05.044.Peer-Reviewed Original ResearchConceptsGenomic classificationProtein-based analysesComplex structural rearrangementsImmune gene expressionMutant RASGene expressionIntegrative analysisFocal amplificationGenomic alterationsStructural rearrangementsProtein expressionMutant BRAFCell markersExpressionGenesRNADNAMutationsCutaneous melanomaKIT mutationsNF1RASRearrangementEnrichmentLandscape