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 ResearchConceptsDevelopmental genesDNA methylation patternsPromoter hypermethylation eventsEpigenetic patternsMethylation gainMethylation patternsMethylation changesHypermethylation eventsEpigenetic changesTissue agingSenescenceMetabolic regulatorTissue typesGenesTransformation potentialCellsHypermethylationRegulatorCancer risk
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 role
2016
Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients
Fu T, Liu Y, Li K, Wan W, Pappou EP, Iacobuzio-Donahue CA, Kerner Z, Baylin SB, Wolfgang CL, Ahuja N. Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients. Oncotarget 2016, 5: 86480-86489. PMID: 27880934, PMCID: PMC5349928, DOI: 10.18632/oncotarget.13441.Peer-Reviewed Original ResearchConceptsDisease-free survivalStage II colorectal cancer patientsStage II CRC patientsCpG island methylator phenotypeMLH1 methylation statusColorectal cancer patientsOverall survivalLymphovascular invasionCRC patientsCancer patientsMucin productionMethylator phenotypeKaplan-Meier analysisPoor clinical outcomeMethylation statusDuodenal adenocarcinomaClinical outcomesAggressive featuresPoor prognosisPrognostic valuePatient subgroupsTumor locationMultivariate analysisPatientsM group
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 status
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 ResearchPrognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and meta-analysis
Juo YY, Johnston FM, Zhang DY, Juo HH, Wang H, Pappou EP, Yu T, Easwaran H, Baylin S, van Engeland M, Ahuja N. Prognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and meta-analysis. Annals Of Oncology 2014, 25: 2314-2327. PMID: 24718889, PMCID: PMC4239805, DOI: 10.1093/annonc/mdu149.Peer-Reviewed Original ResearchConceptsDisease-free survivalCpG island methylator phenotypeColorectal cancer patientsCRC patientsOverall survivalHazard ratioPredictive factorsPrognostic valueCancer patientsPredictive valuePatient disease-free survivalShorter disease-free survivalCancer-specific mortalityAdditional survival benefitMethylator phenotypeShorter overall survivalMicrosatellite instability statusAdjuvant chemotherapyDFS benefitSurvival benefitWorse prognosisCRC prognosisPooled analysisSubgroup analysisNineteen studiesFunctional Identification of Cancer-Specific Methylation of CDO1, HOXA9, and TAC1 for the Diagnosis of Lung Cancer
Wrangle J, Machida EO, Danilova L, Hulbert A, Franco N, Zhang W, Glöckner SC, Tessema M, Van Neste L, Easwaran H, Schuebel KE, Licchesi J, Hooker CM, Ahuja N, Amano J, Belinsky SA, Baylin SB, Herman JG, Brock MV. Functional Identification of Cancer-Specific Methylation of CDO1, HOXA9, and TAC1 for the Diagnosis of Lung Cancer. Clinical Cancer Research 2014, 20: 1856-1864. PMID: 24486589, PMCID: PMC4019442, DOI: 10.1158/1078-0432.ccr-13-2109.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerThree-gene panelLung cancerIndependent cohortPrimary NSCLC samplesCell lung cancerNSCLC cell linesNovel diagnostic biomarkersAdjuvant chemotherapyMolecular diagnostic testsCancer Genome AtlasCancer mortalityCancer-specific methylationSurgical specimensNSCLC samplesMolecular stagingEarly diagnosisDiagnostic biomarkersNormal tissuesDiagnostic testsCohortCancerGenome AtlasMethylation biomarkersCell linesCpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas
Sun L, Guzzetta AA, Fu T, Chen J, Jeschke J, Kwak R, Vatapalli R, Baylin SB, Iacobuzio-Donahue CA, Wolfgang CL, Ahuja N. CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas. Epigenetics 2014, 9: 738-746. PMID: 24518818, PMCID: PMC4063833, DOI: 10.4161/epi.28082.Peer-Reviewed Original ResearchConceptsCpG island methylator phenotypeSporadic duodenal adenomasDuodenal adenomasBRAF mutationsVillous typeMethylator phenotypeCIMP-high statusPeriampullary locationAggressive managementDuodenal adenocarcinomaClinicopathologic featuresColorectal cancerColorectal adenomasKRAS mutationsHigh riskAdenomasMLH1 methylationCIMP statusCancerous lesionsOlder ageP16 methylationTumorsMalignancyInfrequent eventRole of methylation
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 FactorsTranscriptomeThe CpG Island Methylator Phenotype: What's in a Name?
Hughes LA, Melotte V, de Schrijver J, de Maat M, Smit VT, Bovée JV, French PJ, van den Brandt PA, Schouten LJ, de Meyer T, van Criekinge W, Ahuja N, Herman JG, Weijenberg MP, van Engeland M. The CpG Island Methylator Phenotype: What's in a Name? Cancer Research 2013, 73: 5858-5868. PMID: 23801749, DOI: 10.1158/0008-5472.can-12-4306.Peer-Reviewed Original ResearchConceptsCpG island methylator phenotypeTranslocation methylcytosine dioxygenase 2Tumor typesMethylator phenotypePrimary human astrocytesHuman neoplasiaIsocitrate dehydrogenase 1 (IDH1) mutationCpG island promoter methylationColorectal cancerOllier's diseaseAdrenocortical carcinomaProstate cancerMultiple enchondromasHuman astrocytesClinical practiceRenal cellsIDH2 mutationsCancer typesCancerDioxygenase 2Promoter methylationFunction mutationsMafucci's syndromeNeoplasiaLeukemia
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
The CpG island methylator phenotype in colorectal cancer: Progress and problems
Hughes LA, Bakker C, Smits KM, van den Brandt PA, Jonkers D, Ahuja N, Herman JG, Weijenberg MP, van Engeland M. The CpG island methylator phenotype in colorectal cancer: Progress and problems. Biochimica Et Biophysica Acta 2011, 1825: 77-85. PMID: 22056543, DOI: 10.1016/j.bbcan.2011.10.005.Peer-Reviewed Original ResearchConceptsCpG island methylator phenotypeColorectal cancerMethylator phenotypeMolecular pathological epidemiologySporadic colorectal cancerEnvironmental risk factorsPotential clinical importanceMultiple gene panelsOnly original research articlesRisk factorsUnselected seriesInclusion criteriaUnselected casesTrue prevalenceClinical importanceSystematic reviewDisease trendsOriginal research articlesGene panelPrevalenceDistinct subgroupsCancerPrimary causePhenotypeUniversal definitionBreast 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 phenotypeSessile 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
Convergence 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 ResearchConceptsTumor 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
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
2002
DNA Methylation and Environmental Exposures in Human Hepatocellular Carcinoma
Shen L, Ahuja N, Shen Y, Habib NA, Toyota M, Rashid A, Issa JP. DNA Methylation and Environmental Exposures in Human Hepatocellular Carcinoma. Journal Of The National Cancer Institute 2002, 94: 755-761. PMID: 12011226, DOI: 10.1093/jnci/94.10.755.Peer-Reviewed Original Research