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 ResearchMeSH KeywordsAdultAgedColorectal NeoplasmsCpG IslandsDNA MethylationFemaleHumansMaleMiddle AgedMutL Protein Homolog 1Neoplasm StagingPhenotypePrognosisConceptsDisease-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
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 mutation
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
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
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 NeoplasmsCpG island methylator phenotype in colorectal cancer
Toyota M, Ahuja N, Ohe-Toyota M, Herman J, Baylin S, Issa J. CpG island methylator phenotype in colorectal cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8681-8686. PMID: 10411935, PMCID: PMC17576, DOI: 10.1073/pnas.96.15.8681.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAge FactorsCarrier ProteinsCloning, MolecularColorectal NeoplasmsCpG IslandsDNA MethylationDNA RepairGenes, p16Genes, Tumor SuppressorHumansMicrosatellite RepeatsMutL Protein Homolog 1Neoplasm ProteinsNuclear ProteinsPhenotypePolymerase Chain ReactionSulfitesTumor Cells, CulturedConceptsCpG island methylator phenotypeColorectal cancerMethylator phenotypeSporadic colorectal cancerMismatch repair deficiencyCpG islandsAge-dependent mannerNormal colonic cellsCpG island amplificationHigh incidenceColon cancerTHBS1 methylationNormal colonPromoter region CpG islandsSporadic tumorsCancerMicrosatellite instabilityColonic cellsTumor suppressor geneCpG island methylationRepair deficiencyCancer-specific mannerHMLH1 methylationCell linesTranscriptional inactivation
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