2015
New DNA Methylation Markers and Global DNA Hypomethylation Are Associated with Oral Cancer Development
Foy JP, Pickering CR, Papadimitrakopoulou VA, Jelinek J, Lin SH, William WN, Frederick MJ, Wang J, Lang W, Feng L, Zhang L, Kim ES, Fan YH, Hong WK, El-Naggar AK, Lee JJ, Myers JN, Issa JP, Lippman SM, Mao L, Saintigny P. New DNA Methylation Markers and Global DNA Hypomethylation Are Associated with Oral Cancer Development. Cancer Prevention Research 2015, 8: 1027-1035. PMID: 26342026, PMCID: PMC4777304, DOI: 10.1158/1940-6207.capr-14-0179.Peer-Reviewed Original ResearchConceptsGlobal DNA hypomethylationOral squamous cell carcinomaOral premalignant lesionsDNA hypomethylationOral cancer-free survivalCancer-free survivalDNA methylation changesDNA methylation profilesPromoter methylationDNA promoter methylationGlobal DNA methylationTumor suppressor geneNew DNA methylation markersPromoter CpG sitesOSCC developmentDNA methylationMethylation changesMethylation profilesFoxi2Degree of methylationSuppressor geneCpG sitesMethylationDNA methylation markersGenes
2014
Mutational Landscape of Aggressive Cutaneous Squamous Cell Carcinoma
Pickering CR, Zhou JH, Lee JJ, Drummond JA, Peng SA, Saade RE, Tsai KY, Curry JL, Tetzlaff MT, Lai SY, Yu J, Muzny DM, Doddapaneni H, Shinbrot E, Covington KR, Zhang J, Seth S, Caulin C, Clayman GL, El-Naggar AK, Gibbs RA, Weber RS, Myers JN, Wheeler DA, Frederick MJ. Mutational Landscape of Aggressive Cutaneous Squamous Cell Carcinoma. Clinical Cancer Research 2014, 20: 6582-6592. PMID: 25303977, PMCID: PMC4367811, DOI: 10.1158/1078-0432.ccr-14-1768.Peer-Reviewed Original ResearchConceptsAggressive cutaneous squamous cell carcinomaCutaneous squamous cell carcinomaSquamous cell carcinomaCell carcinomaCandidate tumor suppressorNeck squamous cell carcinomaNovel therapeutic targetNovel candidate tumor suppressorTumor suppressorWhole-exome sequencingBone invasionPoor outcomeTherapeutic targetLethal diseaseTumor suppressor geneCarcinomaKMT2C mutationsHigh mutational backgroundGene TP53Mutational landscapePutative linkDriver genesDiseaseMutational spectrumUV exposureKey tumor suppressor genes inactivated by “greater promoter” methylation and somatic mutations in head and neck cancer
Guerrero-Preston R, Michailidi C, Marchionni L, Pickering CR, Frederick MJ, Myers JN, Yegnasubramanian S, Hadar T, Noordhuis MG, Zizkova V, Fertig E, Agrawal N, Westra W, Koch W, Califano J, Velculescu VE, Sidransky D. Key tumor suppressor genes inactivated by “greater promoter” methylation and somatic mutations in head and neck cancer. Epigenetics 2014, 9: 1031-1046. PMID: 24786473, PMCID: PMC4143405, DOI: 10.4161/epi.29025.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellCell Line, TumorCohort StudiesCpG IslandsDNA MethylationFemaleGene SilencingGenes, Tumor SuppressorHead and Neck NeoplasmsHumansMaleMutationPaired Box Transcription FactorsPAX5 Transcription FactorPromoter Regions, GeneticReceptor, Notch1Tumor Suppressor Protein p53ConceptsKey tumor suppressor genesTumor suppressor geneSuppressor geneRecent high-throughput genomic studiesSomatic mutationsPromoter methylationWhole genome gene expression arraysHigh-throughput genomic studiesPax gene familyNovel tumor suppressor geneIntegrated molecular analysisSpecific promoter methylationK methylation arrayGene expression arraysGenome maintenanceEpigenomic levelsGene familyCell fateGenomic studiesDownregulated genesTranscription factorsCanonical NotchEpigenomic alterationsDomain sequencingMethylation arraysSequencing HNC: Emergence of Notch Signaling
Pickering C, Ow T, Myers J. Sequencing HNC: Emergence of Notch Signaling. Current Cancer Research 2014, 303-323. DOI: 10.1007/978-1-4614-8815-6_15.ChaptersTumor suppressor geneSuppressor geneImportant tumor suppressor geneRecent sequencing studiesNeck cancer progressionIdentification of mutationsBiology of headSurprising new findingsNotch signalingGene Notch1Notch pathwaySequencing studiesCancer progressionGenomic abnormalitiesChromosomal alterationsMutationsGenesNotch1PathwayFrequent eventNew lightNeck cancerSignalingBiologyTP53 mutations
2013
Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers
Pickering CR, Zhang J, Yoo SY, Bengtsson L, Moorthy S, Neskey DM, Zhao M, Alves M, Chang K, Drummond J, Cortez E, Xie TX, Zhang D, Chung W, Issa JP, Zweidler-McKay PA, Wu X, El-Naggar AK, Weinstein JN, Wang J, Muzny DM, Gibbs RA, Wheeler DA, Myers JN, Frederick MJ. Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers. Cancer Discovery 2013, 3: 770-781. PMID: 23619168, PMCID: PMC3858325, DOI: 10.1158/2159-8290.cd-12-0537.Peer-Reviewed Original ResearchConceptsOral squamous cell carcinomaCaspase-8Integrative Genomic CharacterizationGenomic alterationsSquamous cell carcinomaComprehensive genomic analysisTumor suppressor geneCopy number changesSomatic driversKey genesGenomic analysisCell carcinomaGene expressionNotch pathwayGenomic characterizationSuppressor geneDriver pathwaysCopy numberPoint mutationsGenesSomatic eventsNumber changesSurvival of patientsOSCC cell linesSubset of head
2011
Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1
Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang J, Wang J, Zhang N, El-Naggar AK, Jasser SA, Weinstein JN, Treviño L, Drummond JA, Muzny DM, Wu Y, Wood LD, Hruban RH, Westra WH, Koch WM, Califano JA, Gibbs RA, Sidransky D, Vogelstein B, Velculescu VE, Papadopoulos N, Wheeler DA, Kinzler KW, Myers JN. Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1. Science 2011, 333: 1154-1157. PMID: 21798897, PMCID: PMC3162986, DOI: 10.1126/science.1206923.Peer-Reviewed Original ResearchMeSH KeywordsCarcinomaCarcinoma, Squamous CellCell Cycle ProteinsCodon, NonsenseExonsF-Box ProteinsF-Box-WD Repeat-Containing Protein 7Gene DosageGenes, p53Genes, Tumor SuppressorHead and Neck NeoplasmsHumansINDEL MutationMutationMutation, MissenseNeoplasms, Squamous CellOligonucleotide Array Sequence AnalysisOncogenesPapillomaviridaePapillomavirus InfectionsReceptor, Notch1Sequence Analysis, DNASmokingSquamous Cell Carcinoma of Head and NeckUbiquitin-Protein LigasesConceptsNeck squamous cell carcinomaSquamous cell carcinomaCell carcinomaHuman papillomavirusHPV-positive tumorsWhole-exome sequencingMore mutationsPrimary tumorCommon cancerMultiple tumorsTobacco useTumor typesTumorsTumor suppressor geneExome sequencingGene copy number analysisNotch1Copy number analysisPatientsCarcinomaInactivating mutationCancerSuppressor geneMutationsGenetic originIndividualizing antimetabolic treatment strategies for head and neck squamous cell carcinoma based on TP53 mutational status
Sandulache VC, Skinner HD, Ow TJ, Zhang A, Xia X, Luchak JM, Wong L, Pickering CR, Zhou G, Myers JN. Individualizing antimetabolic treatment strategies for head and neck squamous cell carcinoma based on TP53 mutational status. Cancer 2011, 118: 711-721. PMID: 21720999, PMCID: PMC3188683, DOI: 10.1002/cncr.26321.Peer-Reviewed Original ResearchConceptsMitochondrial respirationGlycolytic dependenceHNSCC cellsAltered tumor cell metabolismGlycolytic inhibitionTumor suppressor geneTumor cell metabolismTP53 mutational statusMitochondrial reserveInhibition of respirationMetabolic shiftCell metabolismCellular resistanceSuppressor geneHNSCC cell linesMutational statusGlycolytic fluxCell linesRespirationNeck squamous cell carcinomaMutationsGlycolysisCellsClonogenic assayRadioresistance
2006
p16INK4a Modulates p53 in Primary Human Mammary Epithelial Cells
Zhang J, Pickering CR, Holst CR, Gauthier ML, Tlsty TD. p16INK4a Modulates p53 in Primary Human Mammary Epithelial Cells. Cancer Research 2006, 66: 10325-10331. PMID: 17079452, DOI: 10.1158/0008-5472.can-06-1594.Peer-Reviewed Original ResearchConceptsPrimary human mammary epithelial cellsHuman mammary epithelial cellsMammary epithelial cellsCell type-specific regulationTumor suppressor geneStabilization of p53Epithelial cellsP53 protein levelsE2F/Gene activityDownstream targetsCellular responsesSuppressor geneProteolytic degradationProtein levelsP53 proteinP16 proteinP53ProteinReduced levelsP53 statusPathwayCellsGenesRegulation
2001
Is p53 Haploinsufficient for Tumor Suppression? Implications for the p53+/- Mouse Model in Carcinogenicity Testing
Venkatachalam S, Tyner S, Pickering C, Boley S, Recio L, French J, Donehower L. Is p53 Haploinsufficient for Tumor Suppression? Implications for the p53+/- Mouse Model in Carcinogenicity Testing. Toxicologic Pathology 2001, 29: 147-154. PMID: 11695551, DOI: 10.1080/019262301753178555.Peer-Reviewed Original ResearchConceptsEnhanced tumor susceptibilityWild-type p53 alleleP53-deficient miceMouse modelP53 alleleP53 dosageTumor susceptibilityTransgenic mouse modelWild-type littermatesDifferent tumor typesP53 tumor suppressor geneTumor suppressionP53 LOHTumor typesTumorsTumor suppressor geneMiceP53 lossHaploinsufficient tumor suppressorCarcinogenicity testingPreliminary dataOncogenic lesionsCancer formationMechanisms of genotoxicityTumor suppressor