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
2017
Epigenetically altered miR-1247 functions as a tumor suppressor in pancreatic cancer
Yi JM, Kang EJ, Kwon HM, Bae JH, Kang K, Ahuja N, Yang K. Epigenetically altered miR-1247 functions as a tumor suppressor in pancreatic cancer. Oncotarget 2017, 5: 26600-26612. PMID: 28460450, PMCID: PMC5432282, DOI: 10.18632/oncotarget.15722.Peer-Reviewed Original ResearchConceptsCpG island hypermethylationTumor suppressorEctopic expressionPancreatic cancer cellsIsland hypermethylationPancreatic cancer cell linesHuman cancersPutative target genesCancer cell linesNumber of miRNAsChromosome condensation 2Role of miRNAsCell linesMolecular functional roleCancer cellsCpG island methylationPotential tumor suppressorTarget genesEpigenetic alterationsGene expressionMalignant human cancersIsland methylationDirect targetLuciferase reporterFunctional roleDifferential expression of hENT1 and hENT2 in colon cancer cell lines
Liu Y, Zuo T, Zhu X, Ahuja N, Fu T. Differential expression of hENT1 and hENT2 in colon cancer cell lines. Genetics And Molecular Research 2017, 16 PMID: 28218790, DOI: 10.4238/gmr16019549.Peer-Reviewed Original ResearchMeSH KeywordsCaco-2 CellsCell Line, TumorColonic NeoplasmsEquilibrative Nucleoside Transporter 1Equilibrative-Nucleoside Transporter 2Gene ExpressionGene Expression Regulation, NeoplasticHCT116 CellsHumansNeoplasm MetastasisConceptsColon cancer cell linesCancer cell linesMetastatic CRCColorectal cancerHENT1 expressionCell linesHigh hENT1 expressionLow hENT1 expressionMetastatic colorectal cancerNucleoside analoguesHuman equilibrative nucleoside transporter 1Equilibrative nucleoside transporter 1Real-time polymerase chain reactionDrug-based treatmentQuantitative real-time polymerase chain reactionHuman colon cancer cell linesNucleoside transporter 1Clinical responseMost patientsMetastatic cell linesMetastatic sitesMetastatic tumorsTransporter expression profilesPolymerase chain reactionDifferent drug responses
2014
Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers
Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R, Topper MJ, Luo J, Connolly RM, Azad NS, Stearns V, Pardoll DM, Davidson N, Jones PA, Slamon DJ, Baylin SB, Zahnow CA, Ahuja N. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget 2014, 5: 587-598. PMID: 24583822, PMCID: PMC3996658, DOI: 10.18632/oncotarget.1782.Peer-Reviewed Original ResearchMeSH KeywordsAzacitidineCell Line, TumorDNA (Cytosine-5-)-MethyltransferasesDNA, NeoplasmEpigenomicsGene Expression Regulation, NeoplasticHumansNeoplasmsConceptsDNA methyltransferase inhibitorImmune gene setsImmune-stimulatory roleCytokines/chemokinesCancer-testis antigensGene expression subsetsMethyltransferase inhibitorEpigenetic therapyHuman epithelial cancersMechanism of actionCancer cell linesPrimary tumorGene Set Enrichment AnalysisImmunomodulatory pathwaysImmune regulationPotential therapyTestis antigensPatient biopsiesSolid tumorsEpithelial cancersMultiple cancersLow dosesTumor expression dataAntigen processingTherapy
2013
Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer
Yi JM, Guzzetta AA, Bailey VJ, Downing SR, Van Neste L, Chiappinelli KB, Keeley BP, Stark A, Herrera A, Wolfgang C, Pappou EP, Iacobuzio-Donahue CA, Goggins MG, Herman JG, Wang TH, Baylin SB, Ahuja N. Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer. Clinical Cancer Research 2013, 19: 6544-6555. PMID: 24088737, PMCID: PMC4310572, DOI: 10.1158/1078-0432.ccr-12-3224.Peer-Reviewed Original ResearchADAM ProteinsADAMTS1 ProteinBiomarkers, TumorCarcinoma in SituCell Line, TumorCell MovementCell ProliferationCpG IslandsDNADNA MethylationDNA-Binding ProteinsEarly Detection of CancerEpigenesis, GeneticFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMolecular Diagnostic TechniquesPancreatic NeoplasmsPromoter Regions, GeneticProportional Hazards ModelsSensitivity and SpecificitySequence Analysis, DNATranscription FactorsTranscriptome
2012
CpG Island Methylator Phenotype–Positive Tumors in the Absence of MLH1 Methylation Constitute a Distinct Subset of Duodenal Adenocarcinomas and Are Associated with Poor Prognosis
Fu T, Pappou EP, Guzzetta AA, Jeschke J, Kwak R, Dave P, Hooker CM, Morgan R, Baylin SB, Iacobuzio-Donahue CA, Wolfgang CL, Ahuja N. CpG Island Methylator Phenotype–Positive Tumors in the Absence of MLH1 Methylation Constitute a Distinct Subset of Duodenal Adenocarcinomas and Are Associated with Poor Prognosis. Clinical Cancer Research 2012, 18: 4743-4752. PMID: 22825585, PMCID: PMC3482463, DOI: 10.1158/1078-0432.ccr-12-0707.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdenocarcinomaAgedCpG IslandsDNA MethylationDuodenal NeoplasmsFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMaleMicrosatellite InstabilityMiddle AgedMutL Protein Homolog 1Nuclear ProteinsPrognosisProportional Hazards ModelsProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)Ras ProteinsConceptsMLH1 methylation statusDuodenal adenocarcinomaMicrosatellite instabilityPoor prognosisBRAF mutationsMLH1 methylationCox proportional hazards modelDuodenal adenocarcinoma patientsKaplan-Meier analysisSignificant prognostic valueCpG island methylator phenotype (CIMP) statusProportional hazards modelBRAF V600E mutationMethylation statusWorse OSOverall survivalClinicopathologic featuresTumor characteristicsAdenocarcinoma patientsPrognostic valueKRAS mutationsMSI statusHazards modelAdenocarcinomaV600E mutationA 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 statusDNA 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
Sessile serrated adenomas and classical adenomas: An epigenetic perspective on premalignant neoplastic lesions of the gastrointestinal tract
Dhir M, Yachida S, Van Neste L, Glöckner SC, Jeschke J, Pappou EP, Montgomery EA, Herman JG, Baylin SB, Iacobuzio‐Donahue C, Ahuja N. Sessile serrated adenomas and classical adenomas: An epigenetic perspective on premalignant neoplastic lesions of the gastrointestinal tract. International Journal Of Cancer 2011, 129: 1889-1898. PMID: 21154739, PMCID: PMC3206997, DOI: 10.1002/ijc.25847.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdenomaAgedAged, 80 and overCDX2 Transcription FactorColonic PolypsCpG IslandsDiagnosis, DifferentialDNA MethylationFemaleGastrointestinal NeoplasmsGene Expression Regulation, NeoplasticHomeodomain ProteinsHumansHyperplasiaMaleMiddle AgedMutL Protein Homolog 1Nuclear ProteinsPrecancerous ConditionsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsToll-Like Receptor 2ConceptsSessile serrated adenomasHyperplastic polypsMethylation of CDX2Neoplastic lesionsGastrointestinal tractMultiplex methylation-specific PCRSerrated adenomasEarly detectionHIN-1Villous adenomaTubular adenomaClassical adenomasMethylation-specific PCRIRB approvalDiagnostic utilityAdenomasGastrointestinal adenomasHospital pathologyPremalignant adenomasAdenoma samplesCpG island methylation statusInterobserver variabilityTLR2DysplasiaLesions
2009
Prognostic Significance of Gremlin1 (GREM1) Promoter CpG Island Hypermethylation in Clear Cell Renal Cell Carcinoma
van Vlodrop IJ, Baldewijns MM, Smits KM, Schouten LJ, van Neste L, van Criekinge W, van Poppel H, Lerut E, Schuebel KE, Ahuja N, Herman JG, de Bruïne AP, van Engeland M. Prognostic Significance of Gremlin1 (GREM1) Promoter CpG Island Hypermethylation in Clear Cell Renal Cell Carcinoma. American Journal Of Pathology 2009, 176: 575-584. PMID: 20042676, PMCID: PMC2808066, DOI: 10.2353/ajpath.2010.090442.Peer-Reviewed Original ResearchConceptsClear cell renal cell carcinomaCell renal cell carcinomaRenal cell carcinomaCcRCC cell linesCell carcinomaIndependent patient seriesSignificant worse survivalMean vessel densityCell linesOverall survivalWorse survivalClinical outcomesPatient seriesTumor characteristicsPrognostic significanceTumor sizeBone morphogenetic protein antagonistFuhrman gradeMethylation-specific PCRUnivariate analysisVessel densityAngiogenic parametersMultivariate analysisActive angiogenesisTumor angiogenesis
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 statusGenesConvergence of Mutation and Epigenetic Alterations Identifies Common Genes in Cancer That Predict for Poor Prognosis
Chan TA, Glockner S, Yi JM, Chen W, Van Neste L, Cope L, Herman JG, Velculescu V, Schuebel KE, Ahuja N, Baylin SB. Convergence of Mutation and Epigenetic Alterations Identifies Common Genes in Cancer That Predict for Poor Prognosis. PLOS Medicine 2008, 5: e114. PMID: 18507500, PMCID: PMC2429944, DOI: 10.1371/journal.pmed.0050114.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCell Line, TumorColonic NeoplasmsCpG IslandsDNA MethylationEpigenesis, GeneticGene Expression Regulation, NeoplasticHeterozygoteHomozygoteHumansModels, GeneticMutationPrognosisSequence Analysis, DNATreatment OutcomeConceptsTumor suppressor geneUnbiased genome-wide approachSuppressor geneGenome-wide approachesKey tumor suppressor genesBreast cancer cell linesSet of genesCancer cell linesLarge-scale sequencingTumor suppressor statusPromoter CpG island hypermethylationCell linesCpG island hypermethylationTumor-type specificRecent sequencingBiology of cancerEpigenetic eventsCancer genomesEpigenetic analysisEpigenetic alterationsCommon genesTumor suppressorSignificant genesGenetic changesIsland hypermethylation
1999
Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype.
Toyota M, Ahuja N, Suzuki H, Itoh F, Ohe-Toyota M, Imai K, Baylin SB, Issa JP. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Research 1999, 59: 5438-42. PMID: 10554013.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAllelesCarrier ProteinsCpG IslandsCyclin-Dependent Kinase Inhibitor p16Gene Expression Regulation, NeoplasticHumansMethylationModels, GeneticMucous MembraneMutL Protein Homolog 1Neoplasm ProteinsNuclear ProteinsPhenotypePolymerase Chain ReactionStomach Neoplasms