2019
Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood
Eissa MAL, Lerner L, Abdelfatah E, Shankar N, Canner JK, Hasan NM, Yaghoobi V, Huang B, Kerner Z, Takaesu F, Wolfgang C, Kwak R, Ruiz M, Tam M, Pisanic TR, Iacobuzio-Donahue CA, Hruban RH, He J, Wang TH, Wood LD, Sharma A, Ahuja N. Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood. Clinical Epigenetics 2019, 11: 59. PMID: 30953539, PMCID: PMC6451253, DOI: 10.1186/s13148-019-0650-0.Peer-Reviewed Original ResearchConceptsStage IIB diseasePancreatic cancerIIB diseaseStage IIACA 19Stage IBiomarker panelBlood-based biomarker panelPre-operative CA 19Stage I patientsCell-free tumor DNAHigh-risk populationPotential blood biomarkersMost pancreatic cancersBackgroundDespite improvementsCurative resectionSurgical resectionI patientsTwo-gene panelPancreas cancerBlood biomarkersCurative potentialCancer managementAdvanced stageCombination panel
2018
DNA 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 ResearchMeSH KeywordsAnimalsCell Transformation, NeoplasticCellular SenescenceCpG IslandsDNA MethylationEpigenesis, GeneticHumansMiceMice, SCIDNeoplasmsPromoter Regions, GeneticRiskConceptsDevelopmental genesDNA methylation patternsPromoter hypermethylation eventsEpigenetic patternsMethylation gainMethylation patternsMethylation changesHypermethylation eventsEpigenetic changesTissue agingSenescenceMetabolic regulatorTissue typesGenesTransformation potentialCellsHypermethylationRegulatorCancer risk
2017
A Four-Gene Promoter Methylation Marker Panel Consisting of GREM1, NEURL, LAD1, and NEFH Predicts Survival of Clear Cell Renal Cell Cancer Patients
van Vlodrop IJH, Joosten SC, De Meyer T, Smits KM, Van Neste L, Melotte V, Baldewijns MMLL, Schouten LJ, van den Brandt PA, Jeschke J, Yi JM, Schuebel KE, Ahuja N, Herman JG, Aarts MJ, Bosman FT, Van Criekinge W, van Engeland M. A Four-Gene Promoter Methylation Marker Panel Consisting of GREM1, NEURL, LAD1, and NEFH Predicts Survival of Clear Cell Renal Cell Cancer Patients. Clinical Cancer Research 2017, 23: 2006-2018. PMID: 27756787, DOI: 10.1158/1078-0432.ccr-16-1236.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAutoantigensBiomarkers, TumorCarcinoma, Renal CellDisease-Free SurvivalDNA MethylationFemaleHigh-Throughput Nucleotide SequencingHumansIntercellular Signaling Peptides and ProteinsKaplan-Meier EstimateKidney NeoplasmsMaleMiddle AgedNeurofilament ProteinsNon-Fibrillar CollagensOligonucleotide Array Sequence AnalysisPrognosisPromoter Regions, GeneticProportional Hazards ModelsUbiquitin-Protein LigasesConceptsClear cell renal cell carcinomaPrognostic modelNonmetastatic clear cell renal cell carcinomaMethylation markersCox proportional hazards modelPrimary clear cell renal cell carcinomaIndependent patient seriesCause-specific survivalOutcomes of patientsCell renal cell carcinomaPrognosis of patientsKaplan-Meier curvesLog-rank testConfidence intervalsCurrent prognostic modelsRenal cell carcinomaProportional hazards modelClin Cancer ResCcRCC cell linesCancer Genome AtlasClinicopathologic featuresPatient seriesCell carcinomaMethylation-specific PCRPoor survival
2015
Promoter Methylation of CDO1 Identifies Clear-Cell Renal Cell Cancer Patients with Poor Survival Outcome
Deckers IA, Schouten LJ, Van Neste L, van Vlodrop IJ, Soetekouw PM, Baldewijns MM, Jeschke J, Ahuja N, Herman JG, van den Brandt PA, van Engeland M. Promoter Methylation of CDO1 Identifies Clear-Cell Renal Cell Cancer Patients with Poor Survival Outcome. Clinical Cancer Research 2015, 21: 3492-3500. PMID: 25904753, PMCID: PMC4612631, DOI: 10.1158/1078-0432.ccr-14-2049.Peer-Reviewed Original ResearchConceptsCDO1 promoter methylationNetherlands Cohort StudyCysteine dioxygenase type 1Prognostic markerPromoter methylationCcRCC casesRenal cell cancer patientsProspective Netherlands Cohort StudyMultivariate modelRelative prognostic valueKaplan-Meier curvesPopulation-based seriesClear cell renal cell cancer (ccRCC) patientsCurrent prognostic markersPoor survival outcomesConfidence intervalsRelevant prognostic informationIndividual patient outcomesMultivariate HRCohort studyMethylation-specific PCR analysisCancer Genome AtlasPrognostic factorsPrognostic valuePromoter methylation statusEpigenetic 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 cellsPolypeptideSpectrin Repeat Containing Nuclear Envelope 1 and Forkhead Box Protein E1 Are Promising Markers for the Detection of Colorectal Cancer in Blood
Melotte V, Yi JM, Lentjes MH, Smits KM, Van Neste L, Niessen HE, Wouters KA, Louwagie J, Schuebel KE, Herman JG, Baylin SB, van Criekinge W, Meijer GA, Ahuja N, van Engeland M. Spectrin Repeat Containing Nuclear Envelope 1 and Forkhead Box Protein E1 Are Promising Markers for the Detection of Colorectal Cancer in Blood. Cancer Prevention Research 2015, 8: 157-164. PMID: 25538088, PMCID: PMC4316751, DOI: 10.1158/1940-6207.capr-14-0198.Peer-Reviewed Original ResearchAgedArea Under CurveBiomarkers, TumorCell Line, TumorColorectal NeoplasmsCytoskeletal ProteinsDNA MethylationFemaleForkhead Transcription FactorsHumansMaleMiddle AgedNerve Tissue ProteinsNuclear ProteinsPromoter Regions, GeneticReal-Time Polymerase Chain ReactionROC CurveSensitivity and SpecificityTransfection
2014
The promise of methylation on beads for cancer detection and treatment
Guzzetta AA, Pisanic T, Sharma P, Yi JM, Stark A, Wang TH, Ahuja N. The promise of methylation on beads for cancer detection and treatment. Expert Review Of Molecular Diagnostics 2014, 14: 845-852. PMID: 25136840, PMCID: PMC4427839, DOI: 10.1586/14737159.2014.943665.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorColorectal NeoplasmsCpG IslandsDNA MethylationHumansMicrospheresPancreatic NeoplasmsPrecision MedicinePrognosisPromoter Regions, GeneticConceptsChoice of treatment
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 FactorsTranscriptomeCHFR silencing or microsatellite instability is associated with increased antitumor activity of docetaxel or gemcitabine in colorectal cancer
Pelosof L, Yerram SR, Ahuja N, Delmas A, Danilova L, Herman JG, Azad NS. CHFR silencing or microsatellite instability is associated with increased antitumor activity of docetaxel or gemcitabine in colorectal cancer. International Journal Of Cancer 2013, 134: 596-605. PMID: 23873170, PMCID: PMC3830586, DOI: 10.1002/ijc.28390.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBase SequenceCell Cycle ProteinsCell Line, TumorColorectal NeoplasmsDeoxycytidineDNA MethylationDNA PrimersDocetaxelFemaleGemcitabineGene SilencingHumansMiceMicrosatellite InstabilityNeoplasm ProteinsPoly-ADP-Ribose Binding ProteinsPromoter Regions, GeneticReal-Time Polymerase Chain ReactionTaxoidsUbiquitin-Protein LigasesXenograft Model Antitumor AssaysConceptsTumor growth inhibitionColorectal cancerCombination therapyCHFR methylationCell linesAdditive tumor growth inhibitionBiomarker-selected patient populationsMicrosatellite instabilityGrowth inhibitionOngoing clinical trialsCRC cell linesCell line xenograftsMSI-H cell linesCRC patientsChemotherapy responsePatient populationPredictive markerClinical trialsDifferential sensitivityTherapeutic effectHuman xenograftsVivo treatmentMSI statusChemotherapy sensitivityGemcitabine
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
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
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 ResearchMeSH KeywordsBase SequenceColorectal NeoplasmsCpG IslandsDNA MethylationDNA PrimersHumansMutationPromoter Regions, GeneticReverse Transcriptase Polymerase Chain ReactionConceptsTranscriptome-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
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 ResearchMeSH KeywordsBrain NeoplasmsCaco-2 CellsCpG IslandsDNA MethylationGlioblastomaHL-60 CellsHumansJurkat CellsPromoter Regions, GeneticThrombospondin 1Tumor Cells, CulturedConceptsGlioblastoma multiformeTHBS1 expressionThrombospondin-1De novo methylationHuman cancersCell linesPrimary glioblastoma multiformeMethylation-associated inactivationNovo methylationCpG islandsPrimary tumorCpG sitesAngiogenesis inhibitorsTHBS1 methylationMethylation statusMolecular defectsHuman neoplasmsMethylationHuman tumorsDetectable expressionCancerTumorsExpressionCommon featureSilencing
1998
Incidence 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