2023
Deep learning‐based pathology image analysis predicts cancer progression risk in patients with oral leukoplakia
Zhang X, Gleber‐Netto F, Wang S, Martins‐Chaves R, Gomez R, Vigneswaran N, Sarkar A, William W, Papadimitrakopoulou V, Williams M, Bell D, Palsgrove D, Bishop J, Heymach J, Gillenwater A, Myers J, Ferrarotto R, Lippman S, Pickering C, Xiao G. Deep learning‐based pathology image analysis predicts cancer progression risk in patients with oral leukoplakia. Cancer Medicine 2023, 12: 7508-7518. PMID: 36721313, PMCID: PMC10067069, DOI: 10.1002/cam4.5478.Peer-Reviewed Original ResearchConceptsLow-risk groupOral leukoplakiaOL patientsProgression riskOral mucosaHigh-risk patientsOral cancer developmentRisk stratification modelCancer progression riskLarge interobserver variabilityEarly diagnosisHigh riskDysplasia gradingAbnormal morphological featuresOral epitheliumOC developmentEarly interventionLow-risk onesPatientsStratification modelCancer developmentCancer progressionInterobserver variabilityLeukoplakiaRisk
2022
Mildly dysplastic oral lesions with optically-detectable abnormalities share genetic similarities with severely dysplastic lesions
Brenes D, Nipper A, Tan M, Gleber-Netto F, Schwarz R, Pickering C, Williams M, Vigneswaran N, Gillenwater A, Sikora A, Richards-Kortum R. Mildly dysplastic oral lesions with optically-detectable abnormalities share genetic similarities with severely dysplastic lesions. Oral Oncology 2022, 135: 106232. PMID: 36335817, PMCID: PMC9881670, DOI: 10.1016/j.oraloncology.2022.106232.Peer-Reviewed Original ResearchConceptsOral premalignant lesionsMild dysplasiaSevere dysplasiaOral lesionsPremalignant lesionsDysplastic oral lesionsHigh-grade pathologySubset of lesionsLoss of autofluorescenceDysplastic lesionsOptical imaging studiesOral surgeryDysplasiaDetectable abnormalitiesPatient careLesionsImaging studiesEpithelial cell nucleiPatientsGene expressionGene expression profilesMarkersGene expression analysisSimilar gene expressionExpression profilesClinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
Rodriguez CP, Kang H, Geiger JL, Burtness B, Chung CH, Pickering CR, Fakhry C, Le QT, Yom SS, Galloway TJ, Golemis E, Li A, Shoop J, Wong S, Mehra R, Skinner H, Saba NF, Flores ER, Myers JN, Ford JM, Karchin R, Ferris RL, Kunos C, Lynn JM, Malik S. Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. Journal Of The National Cancer Institute 2022, 114: 1619-1627. PMID: 36053203, PMCID: PMC9745425, DOI: 10.1093/jnci/djac163.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaSquamous cell carcinomaClinical trialsCell carcinomaTrial designTP53 mutationsNational Clinical Trials NetworkMetastatic disease settingsClinical trial developmentClinical Trials NetworkNovel therapeutic approachesNational Cancer InstituteMetastatic headTP53-mutated tumorsWorse outcomesClinical studiesFrequent genetic eventTherapeutic approachesCancer InstituteTrial developmentBreakout groupsPatientsDisease settingsBiomarker integrationTrials Network
2020
Functionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma
Gleber‐Netto F, Neskey D, de Mattos Costa A, Kataria P, Rao X, Wang J, Kowalski LP, Pickering CR, Dias‐Neto E, Myers JN. Functionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma. Cancer 2020, 126: 4498-4510. PMID: 32797678, DOI: 10.1002/cncr.33101.Peer-Reviewed Original ResearchConceptsAdvanced oral squamous cell carcinomaOral squamous cell carcinomaExtranodal extensionSquamous cell carcinomaTP53 mutationsAncillary biomarkersCell carcinomaCancer Genome Atlas (TCGA) cohortPostoperative adjuvant therapyTP53 mutation statusWild-type TP53Adjuvant therapyCancer Genome AtlasCommon genetic eventClinicopathologic characteristicsClinical outcomesP53 protein functionPatient managementTreatment decisionsClinical challengeTherapeutic approachesPatientsMutation statusHeterogeneous groupIncreased chance
2019
Identification of novel diagnostic markers for sinonasal undifferentiated carcinoma
Takahashi Y, Gleber‐Netto F, Bell D, Roberts D, Xie T, Abdelmeguid AS, Pickering C, Myers JN, Hanna EY. Identification of novel diagnostic markers for sinonasal undifferentiated carcinoma. Head & Neck 2019, 41: 2688-2695. PMID: 30932264, DOI: 10.1002/hed.25748.Peer-Reviewed Original ResearchConceptsSinonasal squamous cell carcinomaSinonasal undifferentiated carcinomaUndifferentiated carcinomaDiagnostic markerNew diagnostic molecular markersSquamous cell carcinomaDistinct pathologic entityPotential therapeutic targetNovel diagnostic markerNew diagnostic markersSNSCC patientsNeuroendocrine featuresCell carcinomaHistopathologic markersSquamous lineagePathologic entityUndifferentiated tumorsAggressive cancerTumor specimensTherapeutic targetOncology panelUnsupervised cluster analysisCarcinomaPatientsMarkersPredicting Outcome in Head and Neck Cancer: miRNAs with Potentially Big Effects
Clump DA, Pickering CR, Skinner HD. Predicting Outcome in Head and Neck Cancer: miRNAs with Potentially Big Effects. Clinical Cancer Research 2019, 25: 1441-1442. PMID: 30413524, PMCID: PMC6415532, DOI: 10.1158/1078-0432.ccr-18-3078.Peer-Reviewed Original ResearchConceptsHigh-risk patient populationNeck squamous cell carcinomaFive-miRNA signatureSquamous cell carcinomaNovel miRNA signatureCell carcinomaClinical variablesHuman papillomavirusInferior outcomesPatient populationNeck cancerTreatment strategiesPredicting OutcomeMiRNA signatureNegative headOutcomesPatientsCarcinomaPapillomavirusCancerHead
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
APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism
Chen TW, Lee CC, Liu H, Wu CS, Pickering CR, Huang PJ, Wang J, Chang IY, Yeh YM, Chen CD, Li HP, Luo JD, Tan BC, Chan TEH, Hsueh C, Chu LJ, Chen YT, Zhang B, Yang CY, Wu CC, Hsu CW, See LC, Tang P, Yu JS, Liao WC, Chiang WF, Rodriguez H, Myers JN, Chang KP, Chang YS. APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism. Nature Communications 2017, 8: 465. PMID: 28878238, PMCID: PMC5587710, DOI: 10.1038/s41467-017-00493-9.Peer-Reviewed Original ResearchConceptsOral squamous cell carcinomaSquamous cell carcinomaCell carcinomaTaiwanese oral squamous cell carcinomasClinical prognostic relevanceBetter overall survivalCancer prognostic biomarkersExpression of APOBEC3AOverall survivalPrognostic relevanceTaiwanese patientsPrognostic biomarkerSecond cohortGermline polymorphismsCancer typesProminent cancerMutational profileDeletion polymorphismPatientsCarcinomaMutation signaturesExpressionPolymorphismCohortTumors
2015
Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas
Wang Y, Springer S, Mulvey CL, Silliman N, Schaefer J, Sausen M, James N, Rettig EM, Guo T, Pickering CR, Bishop JA, Chung CH, Califano JA, Eisele DW, Fakhry C, Gourin CG, Ha PK, Kang H, Kiess A, Koch WM, Myers JN, Quon H, Richmon JD, Sidransky D, Tufano RP, Westra WH, Bettegowda C, Diaz LA, Papadopoulos N, Kinzler KW, Vogelstein B, Agrawal N. Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Science Translational Medicine 2015, 7: 293ra104. PMID: 26109104, PMCID: PMC4587492, DOI: 10.1126/scitranslmed.aaa8507.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaOral cavity cancerSquamous cell carcinomaTumor DNACell carcinomaOral cavityDetection of HNSCCLate-stage diseaseFraction of patientsPlasma of patientsTumor-specific DNASomatic mutationsHNSCC patientsPatientsValuable biomarkerClinical diagnosisHuman papillomavirus genesCancerSalivaCarcinomaRecurrenceBiomarkersHPVOropharynxHNSCCEvolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients
Osman AA, Neskey DM, Katsonis P, Patel AA, Ward AM, Hsu TK, Hicks SC, McDonald TO, Ow TJ, Alves MO, Pickering CR, Skinner HD, Zhao M, Sturgis EM, Kies MS, El-Naggar A, Perrone F, Licitra L, Bossi P, Kimmel M, Frederick MJ, Lichtarge O, Myers JN. Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients. Cancer Research 2015, 75: 1205-1215. PMID: 25691460, PMCID: PMC4615655, DOI: 10.1158/0008-5472.can-14-2729.Peer-Reviewed Original ResearchConceptsNeck cancer patientsEvolutionary action scoreCancer patientsTP53 mutationsNeck squamous cell carcinomaSquamous cell carcinomaCisplatin-based therapyPlatinum-based therapySubset of headThird of casesNovel scoring systemSurvival benefitProspective evaluationCell carcinomaPlatinum responsePreclinical modelsTreatment selectionAction scoresScoring systemPatientsHNSCCTherapyCoding variantPredictive responseScoresEvolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer
Neskey DM, Osman AA, Ow TJ, Katsonis P, McDonald T, Hicks SC, Hsu TK, Pickering CR, Ward A, Patel A, Yordy JS, Skinner HD, Giri U, Sano D, Story MD, Beadle BM, El-Naggar AK, Kies MS, William WN, Caulin C, Frederick M, Kimmel M, Myers JN, Lichtarge O. Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer. Cancer Research 2015, 75: 1527-1536. PMID: 25634208, PMCID: PMC4383697, DOI: 10.1158/0008-5472.can-14-2735.Peer-Reviewed Original ResearchConceptsTP53 mutationsDistant metastasisP53 mutationsNeck squamous cell carcinomaSquamous cell carcinomaPoor survival outcomesAggressive tumor behaviorEvolutionary action scoreHigh-risk mutationsLung metastasesPrognostic significanceSurvival outcomesCell carcinomaNeck cancerClinical prognosisHigh incidenceLower riskTumor behaviorDecreased survivalKey cellular pathwaysTumor cellsMetastasisRisk mutationsPatientsTumors
2014
Squamous Cell Carcinoma of the Oral Tongue in Young Non-Smokers Is Genomically Similar to Tumors in Older Smokers
Pickering CR, Zhang J, Neskey DM, Zhao M, Jasser SA, Wang J, Ward A, Tsai CJ, Alves M, Zhou JH, Drummond J, El-Naggar AK, Gibbs R, Weinstein JN, Wheeler DA, Wang J, Frederick MJ, Myers JN. Squamous Cell Carcinoma of the Oral Tongue in Young Non-Smokers Is Genomically Similar to Tumors in Older Smokers. Clinical Cancer Research 2014, 20: 3842-3848. PMID: 24874835, PMCID: PMC4102633, DOI: 10.1158/1078-0432.ccr-14-0565.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaOlder patientsOral tongueYounger patientsCell carcinomaWhole-exome sequencingOlder smokersSimilar patientsTongue tumorsNon smokersIncreasing incidenceEpidemiologic studiesIndependent cohortPatientsSCCOTSmokingTumorsCohortAlteration frequencyGenomic effectsTCGA dataCopy number analysisGene-specific mutationsOlder cohortTypes of mutations
2013
High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma
Mroz EA, Tward AD, Pickering CR, Myers JN, Ferris RL, Rocco JW. High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma. Cancer 2013, 119: 3034-3042. PMID: 23696076, PMCID: PMC3735618, DOI: 10.1002/cncr.28150.Peer-Reviewed Original ResearchConceptsMutant-allele tumor heterogeneityNeck squamous cell carcinomaSquamous cell carcinomaHigher mutant allele tumor heterogeneityClinical outcomesCell carcinomaWorse outcomesHigh-risk patientsWorse clinical outcomesOverall survival dataShorter overall survivalAdverse treatment outcomesTumor protein p53 (TP53) mutationsHigh genetic heterogeneityGenetic heterogeneityOverall survivalPrognostic valueAdverse outcomesHuman papillomavirusPatient cohortTreatment outcomesIndividual patientsHigh riskPatientsAdvanced stageBcl-2 Inhibition or FBXW7 Mutation Sensitizes Solid Tumor Cells to HDAC Inhibition In Vitro but Could Prove Difficult to Validate in Patients
Pickering CR, Myers JN. Bcl-2 Inhibition or FBXW7 Mutation Sensitizes Solid Tumor Cells to HDAC Inhibition In Vitro but Could Prove Difficult to Validate in Patients. Cancer Discovery 2013, 3: 258-259. PMID: 23475877, DOI: 10.1158/2159-8290.cd-13-0019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBiphenyl CompoundsCarcinoma, Squamous CellCell Cycle ProteinsF-Box ProteinsF-Box-WD Repeat-Containing Protein 7Histone Deacetylase InhibitorsHistone DeacetylasesHumansMyeloid Cell Leukemia Sequence 1 ProteinNitrophenolsPiperazinesProto-Oncogene Proteins c-bcl-2SulfonamidesUbiquitin-Protein Ligases
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