2024
Spatially Informed Gene Signatures for Response to Immunotherapy in Melanoma.
Aung T, Warrell J, Martinez-Morilla S, Gavrielatou N, Vathiotis I, Yaghoobi V, Kluger H, Gerstein M, Rimm D. Spatially Informed Gene Signatures for Response to Immunotherapy in Melanoma. Clinical Cancer Research 2024, 30: 3520-3532. PMID: 38837895, PMCID: PMC11326985, DOI: 10.1158/1078-0432.ccr-23-3932.Peer-Reviewed Original ResearchGene signatureResistance to immunotherapyResponse to immunotherapyPrediction of treatment outcomeResistant to treatmentAccurate prediction of treatment outcomePredictive of responseImmunotherapy outcomesMelanoma patientsMelanoma specimensValidation cohortPatient stratificationDiscovery cohortTreatment outcomesImmunotherapyMelanomaTumorPatientsCohortS100BOutcomesGene expression dataGenesCD68+macrophagesExpression data
2022
Longitudinal single-cell analysis of a patient receiving adoptive cell therapy reveals potential mechanisms of treatment failure
Qu R, Kluger Y, Yang J, Zhao J, Hafler D, Krause D, Bersenev A, Bosenberg M, Hurwitz M, Lucca L, Kluger H. Longitudinal single-cell analysis of a patient receiving adoptive cell therapy reveals potential mechanisms of treatment failure. Molecular Cancer 2022, 21: 219. PMID: 36514045, PMCID: PMC9749221, DOI: 10.1186/s12943-022-01688-5.Peer-Reviewed Original ResearchConceptsAdoptive cell therapySingle-cell analysisDepth single-cell analysisSingle-cell RNAACT productsDisease progressionT-cell receptor sequencingCell therapyFamily genesFeatures of exhaustionMultiple tumor typesCell expansionGenesNew clonotypesTIL preparationsClonal cell expansionCytokine therapyTreatment failureSerial bloodClonesEffector functionsSerial samplesTumor typesCellular therapyTherapy
2016
Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma.
Bi X, Zhao S, Adeniran A, Kluger H, Xie Z, Nawaf C, Merino M, Valera V, Pantuck A, Said J, Belldegrun A, Lifton R, Shuch B. Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma. Journal Of Clinical Oncology 2016, 34: 509-509. DOI: 10.1200/jco.2016.34.2_suppl.509.Peer-Reviewed Original ResearchDriver genesCancer driver genesSomatic mutationsProtein traffickingIllumina sequencingSomatic cellsGenomic characterizationCell differentiationCell adhesionLoss of heterozygosityClear cell renal cell carcinomaGenesMutational signaturesCell renal cell carcinomaClonal divergenceGenetic alterationsMutationsTP53 mutationsRepair deficiencySarcomatoid transformationSubset of tumorsCcRCCHypermutationRenal cell carcinomaBAP1
2015
Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas
Krauthammer M, Kong Y, Bacchiocchi A, Evans P, Pornputtapong N, Wu C, McCusker JP, Ma S, Cheng E, Straub R, Serin M, Bosenberg M, Ariyan S, Narayan D, Sznol M, Kluger HM, Mane S, Schlessinger J, Lifton RP, Halaban R. Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas. Nature Genetics 2015, 47: 996-1002. PMID: 26214590, PMCID: PMC4916843, DOI: 10.1038/ng.3361.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBenzimidazolesDNA Mutational AnalysisDrug Resistance, NeoplasmExomeGenetic Association StudiesGenetic Predisposition to DiseaseHumansInhibitory Concentration 50Kaplan-Meier EstimateLoss of HeterozygosityMaleMelanomaMutation, MissenseNeurofibromin 1Ras ProteinsSequence Analysis, RNASkin NeoplasmsSunlightTumor Cells, Cultured
2011
Plasma Markers for Identifying Patients with Metastatic Melanoma
Kluger HM, Hoyt K, Bacchiocchi A, Mayer T, Kirsch J, Kluger Y, Sznol M, Ariyan S, Molinaro A, Halaban R. Plasma Markers for Identifying Patients with Metastatic Melanoma. Clinical Cancer Research 2011, 17: 2417-2425. PMID: 21487066, PMCID: PMC3415234, DOI: 10.1158/1078-0432.ccr-10-2402.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntigens, CDBiomarkers, TumorCell Adhesion MoleculesEnzyme-Linked Immunosorbent AssayExtracellular Matrix ProteinsFemaleGlycoproteinsGrowth Differentiation Factor 15HumansIntercellular Adhesion Molecule-1L-Lactate DehydrogenaseMaleMelanomaMiddle AgedNeoplasm MetastasisNeoplasm ProteinsNeoplasm Recurrence, LocalNeoplasm StagingNerve Growth FactorsPrognosisReproducibility of ResultsS100 Calcium Binding Protein beta SubunitS100 ProteinsSensitivity and SpecificityTissue Inhibitor of Metalloproteinase-1ConceptsGenome-wide gene expression dataGene expression dataHigh expression levelsLevels of proteinExpression dataExpression levelsProteinMelanoma cellsStage I/II diseaseEqual-sized trainingMarkersGenesDisease recurrencePlasma markersMetastatic melanomaTIMP-1Lactate dehydrogenaseCEACAMsStage I/II patientsDehydrogenaseOsteopontinStage IV diseaseStage IV patientsMetastatic melanoma patientsGender-matched patients
2006
Rab33A: Characterization, Expression, and Suppression by Epigenetic Modification
Cheng E, Trombetta SE, Kovacs D, Beech RD, Ariyan S, Reyes-Mugica M, McNiff JM, Narayan D, Kluger HM, Picardo M, Halaban R. Rab33A: Characterization, Expression, and Suppression by Epigenetic Modification. Journal Of Investigative Dermatology 2006, 126: 2257-2271. PMID: 16810302, DOI: 10.1038/sj.jid.5700386.Peer-Reviewed Original ResearchConceptsX chromosome-linked geneSpecific gene expressionTranscription initiation siteSpecific promoter regionsMelanoma cellsGTPase mutantsEpigenetic modificationsSmall GTPaseDNA methylationVesicular transportRab33AGene expressionPromoter regionMelanosomal proteinsInitiation siteNormal melanocytesAberrant downregulationGenesEarly eventsAberrant processesMelanocytesExpressionGTPaseImportant roleNormal processCharacterizing disease states from topological properties of transcriptional regulatory networks
Tuck DP, Kluger HM, Kluger Y. Characterizing disease states from topological properties of transcriptional regulatory networks. BMC Bioinformatics 2006, 7: 236. PMID: 16670008, PMCID: PMC1482723, DOI: 10.1186/1471-2105-7-236.Peer-Reviewed Original ResearchConceptsTranscriptional regulatory networksRegulatory networksTranscription factorsTranscriptional networksRegulated genesGene deregulationExpression profilesDiseased statesGene regulatory networksCentrality of genesGene expression experimentsGene expression profilesGene expression studiesGene centralityRegulatory linkExpression experimentsExpression studiesGene linksGenesCell typesExpression datasetsGene subsetsDifferential activityNormal cellsRemarkable degreeAssociation between pathways in regulatory networks
Kluger Y, Kluger H, Tuck D. Association between pathways in regulatory networks. Annual International Conference Of The IEEE Engineering In Medicine And Biology Society (EMBC) 2006, 2006: 2036-2040. PMID: 17946929, DOI: 10.1109/iembs.2006.260730.Peer-Reviewed Original ResearchConceptsRegulatory networksCo-regulated pathwaysHuman regulatory networkRegulatory network connectivityDistinct cell typesTranscriptional regulatory levelCondition-specific networksGene regulationIndividual genesCell statesTranscriptional activityCell typesCell progressionExpression signaturesNumerous pathwaysGene profilesRemarkable connectivityMultiple pathwaysPathwayGenesRegulatory levelsRegulationExpressionCellsNotable differences
2004
Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas
Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E, Trombetta ES, Wu T, Niinobe M, Yoshikawa K, Hannigan GE, Halaban R. Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas. Cancer Research 2004, 64: 5270-5282. PMID: 15289333, DOI: 10.1158/0008-5472.can-04-0731.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCell Transformation, NeoplasticCohort StudiesDown-RegulationGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLymphatic MetastasisMelanocytesMelanomaMiceNuclear ProteinsOligonucleotide Array Sequence AnalysisPrognosisSignal TransductionSkin NeoplasmsSurvival RateTranscription FactorsTransfectionTwist-Related Protein 1Ubiquitin ThiolesteraseConceptsGlobal differential gene expressionMembrane trafficking eventsNovel pathwayNormal melanocytesHelix protein TwistAdditional transcriptional regulatorsDifferential gene expressionMelanoma cellsTransformation of melanocytesCpG promoter methylationNormal human melanocytesTrafficking eventsTranscriptional regulatorsEmbryonic developmentGrowth suppressorChromosomal regionsExpression profilingGene expressionNotch pathwayOligonucleotide microarraysMelanoma tissue microarrayDifferential expressionGenesHuman melanocytesGrowth advantage