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
2014
CpG 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
Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases
Karagkounis G, Torbenson MS, Daniel HD, Azad NS, Diaz LA, Donehower RC, Hirose K, Ahuja N, Pawlik TM, Choti MA. Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. Cancer 2013, 119: 4137-4144. PMID: 24104864, PMCID: PMC3967132, DOI: 10.1002/cncr.28347.Peer-Reviewed Original ResearchConceptsColorectal liver metastasesSurgical therapyBRAF mutationsLiver metastasesKRAS statusPrognostic impactKRAS mutationsMolecular biomarkersThird of patientsRecurrence-free survivalKRAS gene mutationsPrognostic determinantsColorectal metastasesSurgical cohortWorse survivalClinicopathologic factorsIndependent predictorsCancer surgeryClinicopathologic featuresTumor numberPrognostic significanceBRAF analysisColorectal cancerLiver surgeryLower incidence
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