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
2016
Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma
Poruk KE, Valero V, Saunders T, Blackford AL, Griffin JF, Poling J, Hruban RH, Anders RA, Herman J, Zheng L, Rasheed ZA, Laheru DA, Ahuja N, Weiss MJ, Cameron JL, Goggins M, Iacobuzio-Donahue CA, Wood LD, Wolfgang CL. Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma. Annals Of Surgery 2016, 264: 1073-1081. PMID: 26756760, PMCID: PMC4936958, DOI: 10.1097/sla.0000000000001600.Peer-Reviewed Original ResearchConceptsCytokeratin-positive CTCsPancreatic adenocarcinomaMesenchymal markersVimentin-positive CTCsEpithelial tumor cells (ISET) methodFourth leading causeBetter treatment stratificationPortal blood samplesSignificant independent predictorsPotential prognostic biomarkerBiology of metastasisDetection of CTCsSurgical resectionIndependent predictorsPrognostic factorsMedian timeMultivariable analysisPDAC patientsPrognostic utilityCancer deathPatient prognosisLeading causeTreatment stratificationCancer recurrencePoor survivalTumors 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
A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts
Springer S, Wang Y, Dal Molin M, Masica DL, Jiao Y, Kinde I, Blackford A, Raman SP, Wolfgang CL, Tomita T, Niknafs N, Douville C, Ptak J, Dobbyn L, Allen PJ, Klimstra DS, Schattner MA, Schmidt CM, Yip-Schneider M, Cummings OW, Brand RE, Zeh HJ, Singhi AD, Scarpa A, Salvia R, Malleo G, Zamboni G, Falconi M, Jang JY, Kim SW, Kwon W, Hong SM, Song KB, Kim SC, Swan N, Murphy J, Geoghegan J, Brugge W, Castillo C, Mino-Kenudson M, Schulick R, Edil BH, Adsay V, Paulino J, van Hooft J, Yachida S, Nara S, Hiraoka N, Yamao K, Hijioka S, van der Merwe S, Goggins M, Canto MI, Ahuja N, Hirose K, Makary M, Weiss MJ, Cameron J, Pittman M, Eshleman JR, Diaz LA, Papadopoulos N, Kinzler KW, Karchin R, Hruban RH, Vogelstein B, Lennon AM. A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts. Gastroenterology 2015, 149: 1501-1510. PMID: 26253305, PMCID: PMC4782782, DOI: 10.1053/j.gastro.2015.07.041.Peer-Reviewed Original ResearchPersonalized Approaches to Gastrointestinal Cancers Importance of Integrating Genomic Information to Guide Therapy
He J, Ahuja N. Personalized Approaches to Gastrointestinal Cancers Importance of Integrating Genomic Information to Guide Therapy. Surgical Clinics Of North America 2015, 95: 1081-1094. PMID: 26315525, DOI: 10.1016/j.suc.2015.05.002.Peer-Reviewed Original ResearchConceptsGenetic testingPersonalized approachHigh-risk family membersCancer prevention strategiesComplex tumor heterogeneityTherapeutic decision makingProphylactic surgeryClinical trialsPrevention strategiesCancer behaviorGermline mutationsSuch personalized approachesTumor heterogeneityPatientsTherapyFamily membersBiopsySurgeryCancerCliniciansDifferent groupsTrials
2014
Prognostic 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 studiesCpG 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
The 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
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 definition
2000
Distinct 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
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