2024
Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden
Gleber-Netto F, Nagarajan P, Sagiv O, Pickering C, Gross N, Ning J, Yeshi M, Mitku Y, Tetzlaff M, Esmaeli B. Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden. Investigative Ophthalmology & Visual Science 2024, 65: 24. PMID: 38597722, PMCID: PMC11008748, DOI: 10.1167/iovs.65.4.24.Peer-Reviewed Original ResearchConceptsHigh-risk human papillomavirusTumor mutational burdenMutational burdenHistological featuresHigh risk human papillomavirus statusConjunctival squamous cell carcinomaHigh tumor mutational burdenDensity of CD8+PD-L1 expressionTumor-infiltrating lymphocytesCD3+ cellsTumors of patientsSquamous cell carcinomaWhole-exome sequencingPotential treatment strategySCC subtypeThicker tumorsPD-L1CD8+Cell carcinomaHuman papillomavirusCutaneous SCCGenomic alterationsCancer Genome AtlasTreatment strategies
2020
The mutational landscape of early‐ and typical‐onset oral tongue squamous cell carcinoma
Campbell BR, Chen Z, Faden DL, Agrawal N, Li RJ, Hanna GJ, Iyer NG, Boot A, Rozen SG, Vettore AL, Panda B, Krishnan NM, Pickering CR, Myers JN, Guo X, Kuhs K. The mutational landscape of early‐ and typical‐onset oral tongue squamous cell carcinoma. Cancer 2020, 127: 544-553. PMID: 33146897, PMCID: PMC7891879, DOI: 10.1002/cncr.33309.Peer-Reviewed Original ResearchConceptsOral tongue squamous cell carcinomaTongue squamous cell carcinomaSquamous cell carcinomaTongue cancerYounger patientsCell carcinomaTobacco useDriver genesOral tongue cancerPatient-related factorsCancer driver genesTongue cancer specimensAge of onsetMutational landscapeSomatic mutationsMutation signaturesYounger birth cohortsSomatic mutational burdenOlder patientsCancer Genome AtlasSmoking ratesMutational burdenCancer specimensMulticenter consortiumBirth cohortFunctionally 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 chanceIdentifying predictors of HPV‐related head and neck squamous cell carcinoma progression and survival through patient‐derived models
Facompre ND, Rajagopalan P, Sahu V, Pearson AT, Montone KT, James CD, Gleber‐Netto F, Weinstein GS, Jalaly J, Lin A, Rustgi AK, Nakagawa H, Califano JA, Pickering CR, White EA, Windle BE, Morgan IM, Cohen RB, Gimotty PA, Basu D. Identifying predictors of HPV‐related head and neck squamous cell carcinoma progression and survival through patient‐derived models. International Journal Of Cancer 2020, 147: 3236-3249. PMID: 32478869, PMCID: PMC7554059, DOI: 10.1002/ijc.33125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsClass I Phosphatidylinositol 3-KinasesErbB ReceptorsExome SequencingFemaleGenetic Association StudiesHead and Neck NeoplasmsHumansMaleMiceMutationNeoplasm TransplantationPapillomaviridaePapillomavirus E7 ProteinsPapillomavirus InfectionsPatient-Specific ModelingPrognosisSquamous Cell Carcinoma of Head and NeckSurvival AnalysisTNF Receptor-Associated Factor 3ConceptsPatient-derived xenograftsTumor mutational burdenPreclinical modelsMutational burdenHuman papilloma virus-related headHigh tumor mutational burdenNeck squamous cell carcinomaSquamous cell carcinoma progressionNeck squamous cell carcinoma progressionInadequate preclinical modelsSquamous cell carcinomaDisease recurrence riskPatient-derived modelsLow engraftment rateWhole-exome sequencingViral oncogene functionPrognostic alterationsLocal progressionHPV- patientsCancer Genome AtlasCell carcinomaHPV casesPIK3CA mutationsEngraftment rateLethal outcome
2019
Disruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer
Chari NS, Ivan C, Le X, Li J, Mijiti A, Patel AA, Osman AA, Peterson CB, Williams MD, Pickering CR, Caulin C, Myers JN, Calin GA, Lai SY. Disruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer. Journal Of The National Cancer Institute 2019, 112: 266-277. PMID: 31124563, PMCID: PMC7073912, DOI: 10.1093/jnci/djz097.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesChromatin ImmunoprecipitationFeedback, PhysiologicalHead and Neck NeoplasmsHumansMicroRNAsMouth NeoplasmsMutationNeoplasm StagingPromoter Regions, GeneticSquamous Cell Carcinoma of Head and NeckSurvival RateTranscription FactorsTranscription, GeneticTumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsMutant TP53Neck squamous cell carcinomaSquamous cell carcinomaHNSCC cell linesInhibits tumor growthEpidermal growth factor receptorFrequent eventRole of TP53PI3K pathwayGrowth factor receptorCancer Genome AtlasCell carcinomaNeck cancerHNSCC samplesPoor survivalEpidermal growth factorTumor growthVivo findingsTumor progressionPatient samplesTumor samplesTumor survivalTumor cellsNormal tissuesNovel target
2018
High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma
Sandulache VC, Michikawa C, Kataria P, Gleber-Netto FO, Bell D, Trivedi S, Rao X, Wang J, Zhao M, Jasser S, Myers JN, Pickering CR. High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma. Clinical Cancer Research 2018, 24: 1727-1733. PMID: 29330202, PMCID: PMC5884733, DOI: 10.1158/1078-0432.ccr-17-0721.Peer-Reviewed Original ResearchConceptsOral cavity squamous cell carcinomaExtranodal extensionPrimary tumorDisease-free survivalPoor prognostic factorProspective clinical trialsSquamous cell carcinomaAggressive biological phenotypeClin Cancer ResHigh-risk mutationsPersonalized treatment decisionsWild-type TP53ENE statusOSCC dataPN0 tumorsCancer Genome AtlasLymph nodesPrognostic factorsClinical outcomesInstitutional cohortCell carcinomaClinical trialsPoor survivalTreatment decisionsTreatment selection
2016
Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer
Skinner HD, Giri U, Yang L, Woo SH, Story MD, Pickering CR, Byers LA, Williams MD, El-Naggar A, Wang J, Diao L, Shen L, Fan YH, Molkentine DP, Beadle BM, Meyn RE, Myers JN, Heymach JV. Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer. Clinical Cancer Research 2016, 22: 4643-4650. PMID: 27036135, PMCID: PMC5061056, DOI: 10.1158/1078-0432.ccr-15-2785.Peer-Reviewed Original ResearchConceptsHPV-negative HNSCC cell linesHPV-negative HNSCCHNSCC cell linesTargetable biomarkersHuman papillomavirusIndependent cohortCandidate biomarkersPoor disease-free survivalNeck squamous cell carcinomaBiomarker of radioresistanceDisease-free survivalSquamous cell carcinomaDisease-related mortalityMerit further evaluationCell linesFAK inhibitionG2-M arrestFocal adhesion kinaseAdvanced HNSCCWorse DFSCancer Genome AtlasCell carcinomaPharmacologic blockadeCancer subgroupsFAK overexpression
2015
Comprehensive genomic characterization of head and neck squamous cell carcinomas
Lawrence M, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel S, Getz G, Ally A, Balasundaram M, Birol I, Bowlby R, Brooks D, Butterfield Y, Carlsen R, Cheng D, Chu A, Dhalla N, Guin R, Holt R, Jones S, Lee D, Li H, Marra M, Mayo M, Moore R, Mungall A, Gordon Robertson A, Schein J, Sipahimalani P, Tam A, Thiessen N, Wong T, Protopopov A, Santoso N, Lee S, Parfenov M, Zhang J, Mahadeshwar H, Tang J, Ren X, Seth S, Haseley P, Zeng D, Yang L, Xu A, Song X, Pantazi A, Bristow C, Hadjipanayis A, Seidman J, Chin L, Park P, Kucherlapati R, Akbani R, Casasent T, Liu W, Lu Y, Mills G, Motter T, Weinstein J, Diao L, Wang J, Hong Fan Y, Liu J, Wang K, Todd Auman J, Balu S, Bodenheimer T, Buda E, Neil Hayes D, Hoadley K, Hoyle A, Jefferys S, Jones C, Kimes P, Liu Y, Marron J, Meng S, Mieczkowski P, Mose L, Parker J, Perou C, Prins J, Roach J, Shi Y, Simons J, Singh D, Soloway M, Tan D, Veluvolu U, Walter V, Waring S, Wilkerson M, Wu J, Zhao N, Cherniack A, Hammerman P, Tward A, Sekhar Pedamallu C, Saksena G, Jung J, Ojesina A, Carter S, Zack T, Schumacher S, Beroukhim R, Freeman S, Meyerson M, Cho J, Chin L, Getz G, Noble M, DiCara D, Zhang H, Heiman D, Gehlenborg N, Voet D, Lin P, Frazer S, Stojanov P, Liu Y, Zou L, Kim J, Sougnez C, Gabriel S, Lawrence M, Muzny D, Doddapaneni H, Kovar C, Reid J, Morton D, Han Y, Hale W, Chao H, Chang K, Drummond J, Gibbs R, Kakkar N, Wheeler D, Xi L, Ciriello G, Ladanyi M, Lee W, Ramirez R, Sander C, Shen R, Sinha R, Weinhold N, Taylor B, Arman Aksoy B, Dresdner G, Gao J, Gross B, Jacobsen A, Reva B, Schultz N, Onur Sumer S, Sun Y, Chan T, Morris L, Stuart J, Benz S, Ng S, Benz C, Yau C, Baylin S, Cope L, Danilova L, Herman J, Bootwalla M, Maglinte D, Laird P, Triche T, Weisenberger D, Van Den Berg D, Agrawal N, Bishop J, Boutros P, Bruce J, Averett Byers L, Califano J, Carey T, Chen Z, Cheng H, Chiosea S, Cohen E, Diergaarde B, Marie Egloff A, El-Naggar A, Ferris R, Frederick M, Grandis J, Guo Y, Haddad R, Hammerman P, Harris T, Neil Hayes D, Hui A, Jack Lee J, Lippman S, Liu F, McHugh J, Myers J, Kwok Shing Ng P, Perez-Ordonez B, Pickering C, Prystowsky M, Romkes M, Saleh A, Sartor M, Seethala R, Seiwert T, Si H, Tward A, Van Waes C, Waggott D, Wiznerowicz M, Yarbrough W, Zhang J, Zuo Z, Burnett K, Crain D, Gardner J, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton C, Shelton T, Sherman M, Yena P, Black A, Bowen J, Frick J, Gastier-Foster J, Harper H, Leraas K, Lichtenberg T, Ramirez N, Wise L, Zmuda E, Baboud J, Jensen M, Kahn A, Pihl T, Pot D, Srinivasan D, Walton J, Wan Y, Burton R, Davidsen T, Demchok J, Eley G, Ferguson M, Mills Shaw K, Ozenberger B, Sheth M, Sofia H, Tarnuzzer R, Wang Z, Yang L, Claude Zenklusen J, Saller C, Tarvin K, Chen C, Bollag R, Weinberger P, Golusiński W, Golusiński P, Ibbs M, Korski K, Mackiewicz A, Suchorska W, Szybiak B, Wiznerowicz M, Burnett K, Curley E, Gardner J, Mallery D, Penny R, Shelton T, Yena P, Beard C, Mitchell C, Sandusky G, Agrawal N, Ahn J, Bishop J, Califano J, Khan Z, Bruce J, Hui A, Irish J, Liu F, Perez-Ordonez B, Waldron J, Boutros P, Waggott D, Myers J, William W, Lippman S, Egea S, Gomez-Fernandez C, Herbert L, Bradford C, Carey T, Chepeha D, Haddad A, Jones T, Komarck C, Malakh M, McHugh J, Moyer J, Nguyen A, Peterson L, Prince M, Rozek L, Sartor M, Taylor E, Walline H, Wolf G, Boice L, Chera B, Funkhouser W, Gulley M, Hackman T, Neil Hayes D, Hayward M, Huang M, Kimryn Rathmell W, Salazar A, Shockley W, Shores C, Thorne L, Weissler M, Wrenn S, Zanation A, Chiosea S, Diergaarde B, Marie Egloff A, Ferris R, Romkes M, Seethala R, Brown B, Guo Y, Pham M, Yarbrough W. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015, 517: 576-582. PMID: 25631445, PMCID: PMC4311405, DOI: 10.1038/nature14129.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellDNA Copy Number VariationsDNA, NeoplasmFemaleGene Expression Regulation, NeoplasticGenome, HumanGenomicsHead and Neck NeoplasmsHumansMaleMolecular Targeted TherapyMutationOncogenesRNA, NeoplasmSignal TransductionSquamous Cell Carcinoma of Head and NeckTranscription FactorsConceptsNeck squamous cell carcinomaSquamous cell carcinomaCell carcinomaCopy number alterationsMutations of HRASFavorable clinical outcomeFrequent copy number alterationsComprehensive genomic characterizationNumber alterationsFunction TP53 mutationsCancer Genome AtlasSomatic genomic alterationsClinical outcomesLaryngeal tumorsOral cavityFunction alterationsTP53 mutationsCandidate alterationsOncogene PIK3CALoss of TRAF3Novel alterationsCDKN2A inactivationGenome AtlasGenomic alterationsDomain mutations
2013
FXR silencing in human colon cancer by DNA methylation and KRAS signaling
Bailey AM, Zhan L, Maru D, Shureiqi I, Pickering CR, Kiriakova G, Izzo J, He N, Wei C, Baladandayuthapani V, Liang H, Kopetz S, Powis G, Guo GL. FXR silencing in human colon cancer by DNA methylation and KRAS signaling. AJP Gastrointestinal And Liver Physiology 2013, 306: g48-g58. PMID: 24177031, PMCID: PMC3920083, DOI: 10.1152/ajpgi.00234.2013.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBile Acids and SaltsCarcinogenesisCell Line, TumorColonColonic NeoplasmsColonic PolypsDNA MethylationEpithelial-Mesenchymal TransitionGene SilencingHumansNeoplasm StagingProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsReceptors, Cytoplasmic and NuclearSignal TransductionConceptsDNA methylationHuman colon cancerHuman colon cancer progressionMethyl-DNA immunoprecipitationRegulation of FXRFarnesoid X receptorMesenchymal transitionOncogenic signaling cascadesMouse knockout studiesReverse phase protein arrayColon cancer progressionDNA methyltransferase inhibitionFunction of FXRCancer Genome Atlas (TCGA) samplesColon cancer cell linesColon cancer samplesCancer Genome AtlasBisulfite sequencingMethylation patternsKnockout studiesColon cancer developmentSignaling cascadesMethyltransferase inhibitionTumor suppressorPhosphatidylinositol 4