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
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 Research
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
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
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