2019
Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation, Stemness, and Braf V600E-Induced Tumorigenesis
Tao Y, Kang B, Petkovich DA, Bhandari YR, In J, Stein-O'Brien G, Kong X, Xie W, Zachos N, Maegawa S, Vaidya H, Brown S, Yen R, Shao X, Thakor J, Lu Z, Cai Y, Zhang Y, Mallona I, Peinado MA, Zahnow CA, Ahuja N, Fertig E, Issa JP, Baylin SB, Easwaran H. Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation, Stemness, and Braf V600E-Induced Tumorigenesis. Cancer Cell 2019, 35: 315-328.e6. PMID: 30753828, PMCID: PMC6636642, DOI: 10.1016/j.ccell.2019.01.005.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAge FactorsAgingAnimalsCell Transformation, NeoplasticColonic NeoplasmsDNA MethylationGene Expression Regulation, NeoplasticGene SilencingGenetic Predisposition to DiseaseHumansMice, Inbred NODMice, Mutant StrainsMice, SCIDMutationPhenotypeProto-Oncogene Proteins B-rafStem CellsTime FactorsTissue Culture TechniquesWnt Signaling PathwayConceptsCell fate changesPromoter DNA hypermethylationStem-like stateAging-like phenotypesCpG island methylationFate changesDifferentiation defectsEpigenetic abnormalitiesDNA hypermethylationSimultaneous inactivationWnt pathwayWnt activationPromoter hypermethylationTumorigenesisGenesHypermethylationMethylator phenotypeColon tumorigenesisPhenotypeOrganoidsPrecursor roleCRISPRMethylationSupStemness
2016
DNA methylation changes in extracellular remodeling pathway genes during the transformation of human mesenchymal stem cells
Kim T, Park S, Kim H, Ahuja N, Yi J. DNA methylation changes in extracellular remodeling pathway genes during the transformation of human mesenchymal stem cells. Genes & Genomics 2016, 38: 611-617. DOI: 10.1007/s13258-016-0402-x.Peer-Reviewed Original ResearchTranscriptional silencingPathway genesECM genesMesenchymal compartmentStem cell model systemPromoter DNA hypermethylationPromoter hypermethylationDNA methylation changesGene expression profile dataEssential structural componentKey cellular eventsExpression profile dataImportant functional roleExtracellular matrix moleculesColon cancer cell linesCell model systemHuman mesenchymal stem cellsMethylation patternsMethylation changesTranscription-polymerase chain reaction analysisDNA hypermethylationEpigenetic alterationsReverse transcription-polymerase chain reaction analysisHuman malignancesCellular events
2012
A DNA hypermethylation module for the stem/progenitor cell signature of cancer
Easwaran H, Johnstone SE, Van Neste L, Ohm J, Mosbruger T, Wang Q, Aryee MJ, Joyce P, Ahuja N, Weisenberger D, Collisson E, Zhu J, Yegnasubramanian S, Matsui W, Baylin SB. A DNA hypermethylation module for the stem/progenitor cell signature of cancer. Genome Research 2012, 22: 837-849. PMID: 22391556, PMCID: PMC3337430, DOI: 10.1101/gr.131169.111.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorChromatinCluster AnalysisCpG IslandsDNA MethylationEmbryonic Stem CellsEpigenesis, GeneticGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmGenes, RegulatorHistonesHumansMesenchymal Stem CellsNeoplasmsOligonucleotide Array Sequence AnalysisOsteoblastsPolycomb-Group ProteinsPromoter Regions, GeneticRepressor ProteinsSequence Analysis, DNAConceptsEmbryonic stem cellsBivalent chromatinDevelopmental regulatorsPcG target genesKey developmental regulatorsGenome-wide analysisSubset of genesPolycomb repressor complexesStem cellsAdult stem/progenitor cellsStem-like stateStem/progenitor cellsTranscription statePcG genesRepressor complexNormal stem cellsChromatin statusHypermethylated genesTarget genesDNA hypermethylationCancer genesGlobal methylationChromatinGenesMethylation statusTransient Low Doses of DNA-Demethylating Agents Exert Durable Antitumor Effects on Hematological and Epithelial Tumor Cells
Tsai HC, Li H, Van Neste L, Cai Y, Robert C, Rassool FV, Shin JJ, Harbom KM, Beaty R, Pappou E, Harris J, Yen RW, Ahuja N, Brock MV, Stearns V, Feller-Kopman D, Yarmus LB, Lin YC, Welm AL, Issa JP, Minn I, Matsui W, Jang YY, Sharkis SJ, Baylin SB, Zahnow CA. Transient Low Doses of DNA-Demethylating Agents Exert Durable Antitumor Effects on Hematological and Epithelial Tumor Cells. Cancer Cell 2012, 21: 430-446. PMID: 22439938, PMCID: PMC3312044, DOI: 10.1016/j.ccr.2011.12.029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimetabolites, AntineoplasticApoptosisAzacitidineBone Marrow CellsBreast NeoplasmsCell CycleCell Line, TumorCell Transformation, NeoplasticDecitabineDNA DamageDNA MethylationDNA Modification MethylasesGene SilencingHumansLeukemiaMiceMolecular Sequence DataNeoplastic Stem CellsPromoter Regions, GeneticSignal TransductionTumor Cells, CulturedConceptsKey cellular regulatory pathwaysDNA methylation inhibitorPromoter DNA hypermethylationCellular regulatory pathwaysDNA demethylating agentEpithelial tumor cellsPromoter DNA methylationRapid DNA damageCancer stem-like cellsGene reexpressionDNA methylationStem-like cellsMethylation inhibitorDNA hypermethylationRegulatory pathwaysCancer therapy approachesAssociated geneDNA damageTumor cellsImmediate cytotoxicityNanomolar dosesTransient exposureCellsGenesMethylationDNA methylation biomarker candidates for early detection of colon cancer
Yi JM, Dhir M, Guzzetta AA, Iacobuzio-Donahue CA, Heo K, Yang KM, Suzuki H, Toyota M, Kim HM, Ahuja N. DNA methylation biomarker candidates for early detection of colon cancer. Tumor Biology 2012, 33: 363-372. PMID: 22238052, PMCID: PMC3593674, DOI: 10.1007/s13277-011-0302-2.Peer-Reviewed Original ResearchConceptsPromoter DNA hypermethylationCpG island hypermethylationDNA hypermethylationColon cancer cell linesCancer cell linesGene expressionIsland hypermethylationCell linesDNA microarray approachEpigenetic therapeutic targetsGenome-wide platformsPromoter CpG island hypermethylationCancer-specific methylationTumor suppressor geneCancer-specific eventBisulfite sequencingCpG islandsTCERG1LMicroarray approachPromoter regionSuppressor geneGenesColorectal cancer cell linesHuman cancersCommon hallmark
2008
Epigenetic Inactivation of the Canonical Wnt Antagonist SRY-Box Containing Gene 17 in Colorectal Cancer
Zhang W, Glöckner S, Guo M, Machida EO, Wang DH, Easwaran H, Van Neste L, Herman JG, Schuebel KE, Watkins DN, Ahuja N, Baylin SB. Epigenetic Inactivation of the Canonical Wnt Antagonist SRY-Box Containing Gene 17 in Colorectal Cancer. Cancer Research 2008, 68: 2764-2772. PMID: 18413743, PMCID: PMC2823123, DOI: 10.1158/0008-5472.can-07-6349.Peer-Reviewed Original ResearchConceptsGene 17T-cell factor-dependent transcriptionHigh-mobility group transcription factorsFactor-dependent transcriptionMethylation-dependent silencingRegulation of developmentOverexpression of Sox17Cell linesCpG island hypermethylationWnt pathway activityPrecursor cell functionRepression domainHMG boxTranscription factorsDeletion analysisCpG islandsGene silencingDNA hypermethylationGene expressionPromoter regionEpigenetic inactivationCanonical WntGenetic changesIsland hypermethylationSOX17
2007
Comparing the DNA Hypermethylome with Gene Mutations in Human Colorectal Cancer
Schuebel KE, Chen W, Cope L, Glöckner SC, Suzuki H, Yi JM, Chan TA, Van Neste L, Van Criekinge W, van den Bosch S, van Engeland M, Ting AH, Jair K, Yu W, Toyota M, Imai K, Ahuja N, Herman JG, Baylin SB. Comparing the DNA Hypermethylome with Gene Mutations in Human Colorectal Cancer. PLOS Genetics 2007, 3: e157. PMID: 17892325, PMCID: PMC1988850, DOI: 10.1371/journal.pgen.0030157.Peer-Reviewed Original ResearchConceptsTranscriptome-wide approachCpG island DNA hypermethylationHuman colorectal cancer samplesHuman cancer genomesTumor-specific hypermethylationEpigenetic screensTranscriptional silencingIndividual genesCancer genomesEpigenetic changesDNA hypermethylationGene mutationsGenesHypermethylationCell linesIndividual tumorsHuman colorectal cancerColorectal cancer samplesCancer samplesMutationsColorectal cancerCancer biomarkersGenomeSilencingPromoter