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
2018
Epigenetic Pharmacology
Burkhart R, Sharma A, Ahuja N. Epigenetic Pharmacology. 2018, 1551-1575. DOI: 10.1007/978-1-4939-7193-0_69.Peer-Reviewed Original ResearchTranslation of genesHistone modificationsDNA methylationGenetic basisAssociated gene mutationsBiology of diseaseVariety of mechanismsTremendous discoveriesProtein expressionEpigeneticsGene mutationsDecades of researchPancreatic ductal adenocarcinomaEpigenomeMolecular agentsTranscriptionGenesMethylationBiologyMechanismMutationsDuctal adenocarcinomaPotential impactExpressionCurrent research efforts
2017
The Roles of DNA Methylation in the Stages of Cancer
McMahon KW, Karunasena E, Ahuja N. The Roles of DNA Methylation in the Stages of Cancer. The Cancer Journal 2017, 23: 257-261. PMID: 28926425, PMCID: PMC5657558, DOI: 10.1097/ppo.0000000000000279.Peer-Reviewed Original Research
2016
Epigenetic Therapeutics: A New Weapon in the War Against Cancer
Ahuja N, Sharma AR, Baylin SB. Epigenetic Therapeutics: A New Weapon in the War Against Cancer. Annual Review Of Medicine 2016, 67: 73-89. PMID: 26768237, PMCID: PMC4937439, DOI: 10.1146/annurev-med-111314-035900.Peer-Reviewed Original ResearchConceptsEpigenetic therapyPrimary base sequenceNucleosome positioningEpigenetic regulationCellular regulationHeritable patternsEpigenetic mechanismsDNA methylationExplosion of discoveriesGene expressionCancer initiationBase sequenceEpigenomeRegulationFrequent mutationsGenetic abnormalitiesNormal maturationTumor cellsPotent toolChromatinCellsNeoplastic cellsGenesMethylationProteinEpigenetic Pharmacology
Burkhart R, Sharma A, Ahuja N. Epigenetic Pharmacology. 2016, 1-25. DOI: 10.1007/978-1-4939-6631-8_69-1.Peer-Reviewed Original ResearchTranslation of genesHistone modificationsDNA methylationGenetic basisAssociated gene mutationsBiology of diseaseVariety of mechanismsTremendous discoveriesProtein expressionEpigeneticsGene mutationsDecades of researchPancreatic ductal adenocarcinomaEpigenomeMolecular agentsTranscriptionGenesMethylationBiologyMechanismMutationsDuctal adenocarcinomaPotential impactExpressionCurrent research efforts
2013
Frequent Inactivation of Cysteine Dioxygenase Type 1 Contributes to Survival of Breast Cancer Cells and Resistance to Anthracyclines
Jeschke J, O'Hagan HM, Zhang W, Vatapalli R, Calmon MF, Danilova L, Nelkenbrecher C, Van Neste L, Bijsmans IT, Van Engeland M, Gabrielson E, Schuebel KE, Winterpacht A, Baylin SB, Herman JG, Ahuja N. Frequent Inactivation of Cysteine Dioxygenase Type 1 Contributes to Survival of Breast Cancer Cells and Resistance to Anthracyclines. Clinical Cancer Research 2013, 19: 3201-3211. PMID: 23630167, PMCID: PMC3985391, DOI: 10.1158/1078-0432.ccr-12-3751.Peer-Reviewed Original ResearchConceptsBreast cancer cellsEpigenetic eventsDNA methylationGenome-wide DNA methylation analysisCancer cellsDNA methylation-associated silencingKey epigenetic eventsDetoxification of ROSCritical epigenetic eventsComprehensive functional analysisDNA methylation analysisDNA methylation dataMethylation-associated silencingRepressive chromatinOxygen species productionFunctional analysisMethylation dataLevels of ROSMethylation analysisReduced viabilityMissense mutationsFunctional significanceFrequent inactivationSpecies productionMethylation
2012
Transient 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 exposureCellsGenesMethylation
2011
Breast Cancer Methylomes Establish an Epigenomic Foundation for Metastasis
Fang F, Turcan S, Rimner A, Kaufman A, Giri D, Morris LG, Shen R, Seshan V, Mo Q, Heguy A, Baylin SB, Ahuja N, Viale A, Massague J, Norton L, Vahdat LT, Moynahan ME, Chan TA. Breast Cancer Methylomes Establish an Epigenomic Foundation for Metastasis. Science Translational Medicine 2011, 3: 75ra25. PMID: 21430268, PMCID: PMC3146366, DOI: 10.1126/scitranslmed.3001875.Peer-Reviewed Original ResearchConceptsGenome-wide analysisBreast cancer methylomeBreast cancer epigenomeDistinct epigenomic profilesCancer-specific alterationsMetastatic behaviorHuman malignanciesCancer methylomeCancer epigenomeEpigenomic contributionEpigenomic profilesDNA methylationTranscriptomic changesHypermethylator phenotypeMultiple human malignanciesCpG island methylator phenotypeBreast cancer oncogenesisGenesCancer oncogenesisMethylomeMethylationLociLow metastatic riskMetastatic potentialMethylator phenotypeGenomic and Epigenomic Integration Identifies a Prognostic Signature in Colon Cancer
Yi JM, Dhir M, Van Neste L, Downing SR, Jeschke J, Glöckner SC, de Freitas Calmon M, Hooker CM, Funes JM, Boshoff C, Smits KM, van Engeland M, Weijenberg MP, Iacobuzio-Donahue CA, Herman JG, Schuebel KE, Baylin SB, Ahuja N. Genomic and Epigenomic Integration Identifies a Prognostic Signature in Colon Cancer. Clinical Cancer Research 2011, 17: 1535-1545. PMID: 21278247, PMCID: PMC3077819, DOI: 10.1158/1078-0432.ccr-10-2509.Peer-Reviewed Original ResearchConceptsDNA methylationExtracellular matrixDNA methylation analysisEpigenetic mechanismsKey genesEpigenomic alterationsCore pathwaysEpigenetic abnormalitiesPathway genesECM genesMultiple genesEpigenetic alterationsPathway componentsPathway analysisIntegrative analysisLarge CRC cohortsGenesMethylationMethylation analysisSimultaneous methylationPathway disruptionPathwayAggregate roleNovel prognostic biomarkerEVL
2008
Abnormal DNA Methylation of CD133 in Colorectal and Glioblastoma Tumors
Yi JM, Tsai HC, Glöckner S, Lin S, Ohm JE, Easwaran H, James CD, Costello JF, Riggins G, Eberhart CG, Laterra J, Vescovi AL, Ahuja N, Herman JG, Schuebel KE, Baylin SB. Abnormal DNA Methylation of CD133 in Colorectal and Glioblastoma Tumors. Cancer Research 2008, 68: 8094-8103. PMID: 18829568, PMCID: PMC2744404, DOI: 10.1158/0008-5472.can-07-6208.Peer-Reviewed Original ResearchMeSH KeywordsAC133 AntigenAnimalsAntigens, CDAntineoplastic AgentsAzacitidineBrain NeoplasmsCaco-2 CellsCarcinomaColorectal NeoplasmsDecitabineDNA (Cytosine-5-)-MethyltransferasesDNA MethylationFemaleGene DeletionGene Expression Regulation, NeoplasticGlioblastomaGlycoproteinsHCT116 CellsHT29 CellsHumansMiceMice, NudePeptidesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsDNA methylationMethylation patternsPromoter DNA methylation patternsHistone modification marksDNA methylation patternsDNA methylation changesDNA methylation statusPromoter CpG islandsAberrant DNA methylationAbnormal DNA methylationCultured colon cancerStem-like cell populationTranscription stateModification marksPromoter signaturesCpG islandsSuch methylationIndividual cell linesMethylation changesAberrant genesDifferentiated progenyMethylationMarker proteinsMethylation statusGenes
2001
Accelerated age-related CpG island methylation in ulcerative colitis.
Issa JP, Ahuja N, Toyota M, Bronner MP, Brentnall TA. Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Research 2001, 61: 3573-7. PMID: 11325821.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAge FactorsAgedCarrier ProteinsChondroitin Sulfate ProteoglycansColitis, UlcerativeColonic NeoplasmsCpG IslandsDNA MethylationGenes, p16HumansIntestinal MucosaLectins, C-TypeMiddle AgedMutL Protein Homolog 1MyoD ProteinNeoplasm ProteinsNuclear ProteinsPrecancerous ConditionsReceptors, EstrogenVersicansConceptsMechanism of geneP16 exon 1Exon 1CpG island hypermethylationCpG island methylationMethylation marksMethylation patternsUndesirable genesColorectal epithelial cellsIsland hypermethylationIsland methylationGenesMethylationPremature agingMyoDColon cancerHigh-grade dysplasiaEpithelial cellsCell turnoverHypermethylationNon-UC controlsNormal appearing epitheliumUlcerative colitisHigh levelsCSPG2
2000
Aging, methylation and cancer.
Ahuja N, Issa JP. Aging, methylation and cancer. Cellular And Molecular Biology 2000, 15: 835-42. PMID: 10963127, DOI: 10.14670/hh-15.835.Peer-Reviewed Original ResearchConceptsAge-related methylationSuch age-related methylationPromoter-associated CpG islandsTumor suppressor geneGene functionDNA methylationCpG islandsMethylation changesFull methylationGene expressionMethylationGenesNovel targetNormal cellsColon cancerAlternate mechanismMost cancersEvidence pointsFundamental markMyoDIGF2HypermethylationDNAERMutations
1999
Methylation and silencing of the Thrombospondin-1 promoter in human cancer
Li Q, Ahuja N, Burger P, Issa J. Methylation and silencing of the Thrombospondin-1 promoter in human cancer. Oncogene 1999, 18: 3284-3289. PMID: 10359534, DOI: 10.1038/sj.onc.1202663.Peer-Reviewed Original ResearchConceptsGlioblastoma multiformeTHBS1 expressionThrombospondin-1De novo methylationHuman cancersCell linesPrimary glioblastoma multiformeMethylation-associated inactivationNovo methylationCpG islandsPrimary tumorCpG sitesAngiogenesis inhibitorsTHBS1 methylationMethylation statusMolecular defectsHuman neoplasmsMethylationHuman tumorsDetectable expressionCancerTumorsExpressionCommon featureSilencing
1998
Aging and DNA methylation in colorectal mucosa and cancer.
Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP. Aging and DNA methylation in colorectal mucosa and cancer. Cancer Research 1998, 58: 5489-94. PMID: 9850084.Peer-Reviewed Original ResearchConceptsAge-related methylationDNA methylationPromoter-associated CpG islandsDe novo methylationNormal colon mucosaHIC-1Tissue-specific factorsTumor suppressor geneColon mucosaMyoD geneNovo methylationColorectal cancerCpG islandsIGF2 geneSuppressor geneGenesMethylationHypermethylationNormal colonic mucosaAge-related eventsPartial methylationTHBS1Alternate mechanismColorectal mucosaColonic mucosaIncidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma
Herman J, Umar A, Polyak K, Graff J, Ahuja N, Issa J, Markowitz S, Willson J, Hamilton S, Kinzler K, Kane M, Kolodner R, Vogelstein B, Kunkel T, Baylin S. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 6870-6875. PMID: 9618505, PMCID: PMC22665, DOI: 10.1073/pnas.95.12.6870.Peer-Reviewed Original ResearchConceptsCpG islandsMismatch repair genesCell linesDNA mismatch repairMMR-deficient cell linesDNA methylationSuch methylationSporadic primary colorectal cancerEpigenetic inactivationMMR capacityMismatch repairRepair genesMethylationFunctional consequencesColorectal cancer cell linesCancer cell linesPromoter hypermethylationHypermethylationMicrosatellite instabilityProtein expressionHMLH1 proteinGenesColorectal cancerHMLH1 protein expressionInactivation
1997
Association between CpG island methylation and microsatellite instability in colorectal cancer.
Ahuja N, Mohan AL, Li Q, Stolker JM, Herman JG, Hamilton SR, Baylin SB, Issa JP. Association between CpG island methylation and microsatellite instability in colorectal cancer. Cancer Research 1997, 57: 3370-4. PMID: 9269998.Peer-Reviewed Original ResearchConceptsDe novo methylationNovo methylationPromoter region CpG islandsThrombospondin-1 genesCpG island methylationDeficient DNA repairCancer 1 geneMethylation patternsTranscriptional inactivationCpG islandsDNA repairImportant genesHypermethylation eventsColorectal cancerGenetic instabilityExtensive methylationIsland methylationGenesMethylationAberrant methylationRepair genesInsulin-like growth factor IIPromoter hypermethylationMicrosatellite instabilityGrowth factor II