2019
PDK1 Mediates NOTCH1-Mutated Head and Neck Squamous Carcinoma Vulnerability to Therapeutic PI3K/mTOR Inhibition
Sambandam V, Frederick MJ, Shen L, Tong P, Rao X, Peng S, Singh R, Mazumdar T, Huang C, Li Q, Pickering CR, Myers JN, Wang J, Johnson FM. PDK1 Mediates NOTCH1-Mutated Head and Neck Squamous Carcinoma Vulnerability to Therapeutic PI3K/mTOR Inhibition. Clinical Cancer Research 2019, 25: 3329-3340. PMID: 30770351, PMCID: PMC6548600, DOI: 10.1158/1078-0432.ccr-18-3276.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCell ProliferationCRISPR-Cas SystemsDisease Models, AnimalDose-Response Relationship, DrugGene EditingGene ExpressionGene Knockdown TechniquesHumansLoss of Function MutationMicePhosphatidylinositol 3-KinasesProtein Kinase InhibitorsPyruvate Dehydrogenase Acetyl-Transferring KinaseReceptor, Notch1Signal TransductionSquamous Cell Carcinoma of Head and NeckTOR Serine-Threonine KinasesConceptsPI3K/mTOR inhibitorPI3K/mTOR inhibitionPI3K/mTOR pathway inhibitorsMTOR pathway inhibitorsHNSCC cell linesMTOR inhibitorsMTOR inhibitionCell linesPathway inhibitorNeck squamous cell carcinomaDrug-sensitive cell linesClinical response ratePI3K/mTOR pathwaySquamous cell carcinomaBiomarkers of responseOrthotopic xenograft modelCell carcinomaTumor sizeXenograft modelHNSCCSingle agentPDK1 overexpressionResponse rateMolecular vulnerabilitiesPharmacogenomic approach
2018
Mutation allele frequency threshold does not affect prognostic analysis using next-generation sequencing in oral squamous cell carcinoma
Ma J, Fu Y, Tu YY, Liu Y, Tan YR, Ju WT, Pickering CR, Myers JN, Zhang ZY, Zhong LP. Mutation allele frequency threshold does not affect prognostic analysis using next-generation sequencing in oral squamous cell carcinoma. BMC Cancer 2018, 18: 758. PMID: 30041611, PMCID: PMC6057048, DOI: 10.1186/s12885-018-4481-8.Peer-Reviewed Original ResearchConceptsOral squamous cell carcinomaSquamous cell carcinomaPrognostic analysisOSCC patientsCell carcinomaMethodsForty-six patientsClinical outcome analysisNext-generation sequencingAllele frequency thresholdWild-type genotypeParaffin-embedded tissuesNon-synonymous mutationsAllele frequenciesClinical outcomesOutcome analysisPatientsPanel of cancerType genotypeSignificant differencesCarcinomaFrequency thresholdNotch1CDKN2AMutationsCASP8
2017
Distinct pattern of TP53 mutations in human immunodeficiency virus–related head and neck squamous cell carcinoma
Gleber‐Netto F, Zhao M, Trivedi S, Wang J, Jasser S, McDowell C, Kadara H, Zhang J, Wang J, William WN, Lee JJ, Nguyen ML, Pai SI, Walline HM, Shin DM, Ferris RL, Carey TE, Myers JN, Pickering CR, Consortium F. Distinct pattern of TP53 mutations in human immunodeficiency virus–related head and neck squamous cell carcinoma. Cancer 2017, 124: 84-94. PMID: 29053175, PMCID: PMC5785080, DOI: 10.1002/cncr.31063.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCadherinsCarcinoma, Squamous CellCase-Control StudiesCaspase 8Class I Phosphatidylinositol 3-KinasesCyclin D1Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18ErbB ReceptorsF-Box-WD Repeat-Containing Protein 7FemaleHead and Neck NeoplasmsHistone MethyltransferasesHistone-Lysine N-MethyltransferaseHIV InfectionsHLA-A AntigensHumansIn Situ HybridizationIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1LIM Domain ProteinsMaleMiddle AgedNF-E2-Related Factor 2Nuclear ProteinsPapillomaviridaePapillomavirus InfectionsProtein Serine-Threonine KinasesProto-Oncogene Proteins p21(ras)Receptor, Notch1Receptor, Notch2Receptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSquamous Cell Carcinoma of Head and NeckTranscription FactorsTumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsHuman immunodeficiency virus-infected individualsHuman immunodeficiency virus (HIV) infectionNeck squamous cell carcinomaHuman papillomavirus (HPV) statusImmunodeficiency virus infectionVirus-infected individualsSquamous cell carcinomaSample of HIVTP53 mutation frequencyHNSCC patientsCell carcinomaHistopathological differencesPolymerase chain reactionIon Reporter softwareP16 immunostainingDistinct biologyVirus infectionHigh incidenceHIVHNSCCMultiplex polymerase chain reactionDistinct patternsHIV virusTumor samplesTP53 gene
2014
Key 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 arrays
2012
Lessons learned from next‐generation sequencing in head and neck cancer
Loyo M, Li RJ, Bettegowda C, Pickering CR, Frederick MJ, Myers JN, Agrawal N. Lessons learned from next‐generation sequencing in head and neck cancer. Head & Neck 2012, 35: 454-463. PMID: 22907887, PMCID: PMC3715072, DOI: 10.1002/hed.23100.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellClass I Phosphatidylinositol 3-KinasesCyclin-Dependent Kinase Inhibitor p16DNA Mutational AnalysisGenetic Predisposition to DiseaseHead and Neck NeoplasmsHumansMutationPhosphatidylinositol 3-KinasesProto-Oncogene Proteins p21(ras)Receptor, Notch1Squamous Cell Carcinoma of Head and NeckTumor Suppressor Protein p53ConceptsNeck cancerSquamous cell carcinomaNext-generation sequencingPotential therapeutic interventionsCell carcinomaHuman papillomavirusClinical correlationTherapeutic interventionsCancerCommon mutationsMutation patternsCurrent reviewMutational spectrumNotch1Whole exome captureCellular pathwaysHead
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 origin