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 effortsDNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk
Xie W, Kagiampakis I, Pan L, Zhang YW, Murphy L, Tao Y, Kong X, Kang B, Xia L, Carvalho FLF, Sen S, Yen R, Zahnow CA, Ahuja N, Baylin SB, Easwaran H. DNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk. Cancer Cell 2018, 33: 309-321.e5. PMID: 29438699, PMCID: PMC5813821, DOI: 10.1016/j.ccell.2018.01.008.Peer-Reviewed Original ResearchConceptsDevelopmental genesDNA methylation patternsPromoter hypermethylation eventsEpigenetic patternsMethylation gainMethylation patternsMethylation changesHypermethylation eventsEpigenetic changesTissue agingSenescenceMetabolic regulatorTissue typesGenesTransformation potentialCellsHypermethylationRegulatorCancer risk
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 cellsGenesMethylationProteinChapter 11 Prognostic Epigenetics
Sharma A, Abdelfatah E, Al Eissa M, Ahuja N. Chapter 11 Prognostic Epigenetics. 2016, 177-195. DOI: 10.1016/b978-0-12-803239-8.00011-9.Peer-Reviewed Original ResearchEpigenetic 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
2015
Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in breast cancer
Calmon MF, Jeschke J, Zhang W, Dhir M, Siebenkäs C, Herrera A, Tsai HC, O'Hagan HM, Pappou EP, Hooker CM, Fu T, Schuebel KE, Gabrielson E, Rahal P, Herman JG, Baylin SB, Ahuja N. Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in breast cancer. Epigenetics 2015, 10: 622-632. PMID: 25985363, PMCID: PMC4622480, DOI: 10.1080/15592294.2015.1050173.Peer-Reviewed Original ResearchConceptsNeurofilament medium polypeptideNeurofilament heavy polypeptideDNA methylation-associated silencingDNA methylation-mediated silencingNeurofilament genesMethylation-mediated silencingMethylation-associated silencingMethylation-mediated inactivationGo/G1 phaseEpigenetic silencingMedium polypeptideEpigenetic inactivationCell cycleMajor subunitBreast cancer cellsCell typesGenesSilencingHeavy polypeptideG1 phaseFunctional significanceCandidate DNAMature neuronsCancer cellsPolypeptide
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
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
2010
The role of oncogenes in gastrointestinal cancer.
Pappou EP, Ahuja N. The role of oncogenes in gastrointestinal cancer. Gastrointestinal Cancer Research : GCR 2010, s2-s15. PMID: 21472044, PMCID: PMC3047044.Peer-Reviewed Original ResearchActive chromatin domainsComplex regulatory cascadeGrowth regulatory genesProducts of oncogenesRole of oncogenesChromatin remodelersChromatin domainsRegulatory cascadeOncogene researchTranscription factorsChimeric geneGrowth factor receptorSignal transducerCell cycleMolecular mechanismsProtein productsApoptosis regulatorInappropriate expressionDifferent promotersMolecular biologyOncogene activationGenesNormal developmentPoint mutationsActive oncogenes
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
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
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. Histology And Histopathology 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 markMyoDIGF2HypermethylationDNAERMutationsDistinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype
Toyota M, Ohe-Toyota M, Ahuja N, Issa J. Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 710-715. PMID: 10639144, PMCID: PMC15395, DOI: 10.1073/pnas.97.2.710.Peer-Reviewed Original ResearchMeSH KeywordsAdenomaBase SequenceColorectal NeoplasmsCpG IslandsDNA MethylationDNA Mutational AnalysisDNA, NeoplasmGenes, p16Genes, p53Genes, rasHumansMicrosatellite RepeatsMutationPhenotypePoint MutationPolymorphism, Single-Stranded ConformationalProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSequence DeletionTumor Cells, CulturedConceptsCpG island methylator phenotypeColorectal cancerK-RAS mutationsDifferent genetic lesionsActivation of oncogenesTumor suppressor geneMultiple CpG islandsColorectal tumorsMethylator phenotypeCpG islandsDistinct genetic profilesP53 mutationsEpigenetic alterationsMolecular diversitySuppressor geneGenetic lesionsNovel pathwayGroup of tumorsGenetic alterationsK-RASMutationsCancer developmentSimultaneous methylationGenes
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