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 incidenceKRAS G>A mutation favors poor tumor differentiation but may not be associated with prognosis in patients with curatively resected duodenal adenocarcinoma
Fu T, Guzzetta AA, Jeschke J, Vatapalli R, Dave P, Hooker CM, Morgan R, Iacobuzio‐Donahue C, Liu B, Ahuja N. KRAS G>A mutation favors poor tumor differentiation but may not be associated with prognosis in patients with curatively resected duodenal adenocarcinoma. International Journal Of Cancer 2013, 132: 2502-2509. PMID: 23065691, PMCID: PMC3579006, DOI: 10.1002/ijc.27910.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBiomarkers, TumorCell DifferentiationDNA, NeoplasmDuodenal NeoplasmsFemaleHumansMaleMicrosatellite RepeatsMiddle AgedMutationNeoplasm Recurrence, LocalNeoplasm StagingPolymerase Chain ReactionPrognosisProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsSurvival RateConceptsPoor tumor differentiationKRAS GPositive lymph nodesDuodenal adenocarcinomaKRAS mutationsTumor differentiationMutation carriersDistant relapseLymph nodesMultivariate logistic regression analysisShorter relapse-free survivalFuture staging systemsRelapse-free survivalShorter overall survivalPossible prognostic roleLogistic regression analysisCurative resectionPoor OSOverall survivalPrognostic roleTumor characteristicsClinical outcomesClinicopathological characteristicsPoor prognosisPrognostic significance
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