2021
Tumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF
Cheok SK, Narayan A, Arnal-Estape A, Gettinger S, Goldberg SB, Kluger HM, Nguyen D, Patel A, Chiang V. Tumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF. JCO Precision Oncology 2021, 5: 163-172. PMID: 34250381, PMCID: PMC8232069, DOI: 10.1200/po.20.00292.Peer-Reviewed Original ResearchConceptsIntraparenchymal brain metastasesBrain metastasesCell-free DNAExtracranial tumorsBrain metastasis tissuesProgressive brain metastasesThird of patientsNormal pressure hydrocephalusTumor DNA mutationsPrimary cancer typeAnalysis of CSFSamples of CSFLeptomeningeal diseaseEffective surrogate markerBrain biopsyPressure hydrocephalusLumbar punctureSurrogate markerCancer-associated genesMetastasis tissuesPatientsMetastasisDiscordant responsesRenal cellsGenomic profiling
2016
Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma
Bi M, Zhao S, Said JW, Merino MJ, Adeniran AJ, Xie Z, Nawaf CB, Choi J, Belldegrun AS, Pantuck AJ, Kluger HM, Bilgüvar K, Lifton RP, Shuch B. Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 2170-2175. PMID: 26864202, PMCID: PMC4776463, DOI: 10.1073/pnas.1525735113.Peer-Reviewed Original ResearchMeSH KeywordsAgedCarcinoma, Renal CellCell DedifferentiationDNA Mismatch RepairDNA-Binding ProteinsExomeFemaleGenes, p53HumansKidney NeoplasmsLoss of HeterozygosityMaleMiddle AgedMutationNuclear ProteinsOncogenesPolymorphism, Single NucleotidePrognosisTranscription FactorsTumor Suppressor ProteinsUbiquitin ThiolesteraseConceptsClear cell renal cell carcinomaCell renal cell carcinomaRenal cell carcinomaSarcomatoid elementsCarcinomatous elementsCell carcinomaSomatic single nucleotide variantsVon Hippel-Lindau tumor suppressorPoor-prognosis cancerTreatment of patientsTumor protein p53 (TP53) mutationsMismatch repair deficiencyRich interaction domain 1ASarcomatoid featuresPoor prognosisUnknown pathogenesisPolybromo-1TP53 mutationsP53 mutationsSarcomatoid transformationPan-cancer genesExome sequencingTumorsRepair deficiencyProtein 1Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma
Wilson MA, Zhao F, Khare S, Roszik J, Woodman SE, D'Andrea K, Wubbenhorst B, Rimm DL, Kirkwood JM, Kluger HM, Schuchter LM, Lee SJ, Flaherty KT, Nathanson KL. Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma. Clinical Cancer Research 2016, 22: 374-382. PMID: 26307133, PMCID: PMC4821426, DOI: 10.1158/1078-0432.ccr-15-1162.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsCarboplatinDisease-Free SurvivalDNA Copy Number VariationsDNA Mutational AnalysisDouble-Blind MethodGenes, rasHumansMelanomaMutationNeoplasm StagingNiacinamidePaclitaxelPhenylurea CompoundsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-metSorafenibTreatment OutcomeConceptsProgression-free survivalGene copy gainOverall survivalImproved progression-free survivalCopy gainImproved overall survivalGenomic alterationsCancer Genome Atlas (TCGA) datasetImproved treatment responseClinical outcomesMET amplificationV600KCCND1 amplificationTreatment responseMelanoma pathogenesisV600E mutationCurrent FDAPretreatment samplesBRAF geneTumor samplesPatientsSorafenibTherapyTumorsAtlas dataset
2014
Correlation of Somatic Mutations and Clinical Outcome in Melanoma Patients Treated with Carboplatin, Paclitaxel, and Sorafenib
Wilson MA, Zhao F, Letrero R, D'Andrea K, Rimm DL, Kirkwood JM, Kluger HM, Lee SJ, Schuchter LM, Flaherty KT, Nathanson KL. Correlation of Somatic Mutations and Clinical Outcome in Melanoma Patients Treated with Carboplatin, Paclitaxel, and Sorafenib. Clinical Cancer Research 2014, 20: 3328-3337. PMID: 24714776, PMCID: PMC4058354, DOI: 10.1158/1078-0432.ccr-14-0093.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinDouble-Blind MethodFemaleFollow-Up StudiesGenotypeGTP PhosphohydrolasesHumansMaleMelanomaMembrane ProteinsMiddle AgedMutationNeoplasm StagingNiacinamidePaclitaxelPhenylurea CompoundsPrognosisProto-Oncogene Proteins B-rafSkin NeoplasmsSorafenibSurvival RateConceptsProgression-free survivalNRAS-mutant melanomaPlatelet-derived growth factor receptorPerformance statusClinical outcomesNRAS mutationsCox proportional hazards modelVEGF receptorsSomatic mutationsWorse performance statusGood performance statusImproved clinical responseKaplan-Meier methodClinical trial populationsPretreatment tumor samplesSite of diseaseProportional hazards modelEffect of sorafenibBRAF-mutant melanomaFisher's exact testGrowth factor receptorClinical responseOverall survivalClinicopathologic featuresMelanoma patientsMEK targeting in N-RAS mutated metastatic melanoma
Thumar J, Shahbazian D, Aziz SA, Jilaveanu LB, Kluger HM. MEK targeting in N-RAS mutated metastatic melanoma. Molecular Cancer 2014, 13: 45. PMID: 24588908, PMCID: PMC3945937, DOI: 10.1186/1476-4598-13-45.Peer-Reviewed Original ResearchConceptsN-RASShort-term cultureMelanoma patientsMelanoma culturesYale Cancer CenterMetastatic melanoma patientsTime of presentationOngoing clinical trialsProtein kinase pathway activationN-RAS mutationsB-RafPan-RAF inhibitorTerm cultureKinase pathway activationConclusionsThe prognosisBrain metastasesClinical characteristicsMetastatic diseasePathologic dataWorse prognosisCancer CenterMetastatic melanomaClinical trialsMutant melanomaMelanoma cell cultures
2013
Radiation sensitivity and sensitization in melanoma
Shahbazian D, Bindra RS, Kluger HM, Glazer PM. Radiation sensitivity and sensitization in melanoma. Pigment Cell & Melanoma Research 2013, 26: 928-930. PMID: 23870422, PMCID: PMC3866027, DOI: 10.1111/pcmr.12147.Peer-Reviewed Original ResearchAdvances in the systemic treatment of metastatic melanoma.
Yushak M, Kluger HM, Sznol M. Advances in the systemic treatment of metastatic melanoma. Oncology 2013, 27: 374-81. PMID: 25184258, PMCID: PMC6092183.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalDrug Therapy, CombinationHumansImidazolesImmunologic FactorsImmunotherapy, AdoptiveIndolesIpilimumabMelanomaMutationNivolumabOximesProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins B-rafPyridonesPyrimidinonesSkin NeoplasmsSulfonamidesVemurafenibConceptsMetastatic melanomaTumor-host immune interactionsRandomized phase III trialPhase III trialsCombination of dabrafenibAdoptive cell therapyStandard of carePromising new agentPhase II dataIII trialsOverall survivalSystemic treatmentPredictive biomarkersMechanisms of resistanceTreatment outcomesIndividual patientsLimited efficacyAvailable agentsImmune interactionsNew agentsMolecular alterationsEffective agentCell therapyCurrent agentsMelanoma cells
2012
Integrated analysis of tumor samples sheds light on tumor heterogeneity.
Parisi F, Micsinai M, Strino F, Ariyan S, Narayan D, Bacchiocchi A, Cheng E, Xu F, Li P, Kluger H, Halaban R, Kluger Y. Integrated analysis of tumor samples sheds light on tumor heterogeneity. The Yale Journal Of Biology And Medicine 2012, 85: 347-61. PMID: 23012583, PMCID: PMC3447199.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorChromosome MappingChromosomes, HumanDNA Copy Number VariationsEvolution, MolecularGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmHumansIntercellular Signaling Peptides and ProteinsKaryotypingMelanomaMutationOligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotideProto-Oncogene Proteins B-rafConceptsHigh-throughput profilingGene expression levelsExpression levelsDifferent gene expression levelsGene expression profilingCopy number analysisExpression profilingSNP arrayPathway analysisCopy number statusWnt pathwayTumor samplesNumber alteration profilesTumor heterogeneityTumor evolutionCopy number alteration profilesGenomic aberrationsIntegrated analysisCell linesTumor subclonesNumber analysisNumber statusProfilingDriver mutationsRecurrent associationExome sequencing identifies recurrent somatic RAC1 mutations in melanoma
Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker J, Cheng E, Davis MJ, Goh G, Choi M, Ariyan S, Narayan D, Dutton-Regester K, Capatana A, Holman EC, Bosenberg M, Sznol M, Kluger HM, Brash DE, Stern DF, Materin MA, Lo RS, Mane S, Ma S, Kidd KK, Hayward NK, Lifton RP, Schlessinger J, Boggon TJ, Halaban R. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nature Genetics 2012, 44: 1006-1014. PMID: 22842228, PMCID: PMC3432702, DOI: 10.1038/ng.2359.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overCase-Control StudiesDNA Mutational AnalysisExomeFemaleGene FrequencyGenetic Predisposition to DiseaseHumansMaleMelanomaMiddle AgedModels, MolecularMutationProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)Rac1 GTP-Binding ProteinSequence Analysis, DNASkin NeoplasmsUveal NeoplasmsConceptsSun-exposed melanomasDriver Mutations in Melanoma: Lessons Learned From Bench-to-Bedside Studies
Mehnert JM, Kluger HM. Driver Mutations in Melanoma: Lessons Learned From Bench-to-Bedside Studies. Current Oncology Reports 2012, 14: 449-457. PMID: 22723080, PMCID: PMC4447200, DOI: 10.1007/s11912-012-0249-5.Peer-Reviewed Original ResearchConceptsDriver mutationsSpecific patient subsetsPotential therapeutic strategyPatient subsetsSomatic driver mutationsMetastatic melanomaBedside studiesUveal melanomaTherapeutic strategiesBRAFV600E mutationMalignant transformationMelanomaMolecular classificationDevelopment of inhibitorsHuman samplesMutationsMolecular biologyBRAFDisease
2011
Molecular Alternations in Uveal Melanoma
Materin MA, Faries M, Kluger HM. Molecular Alternations in Uveal Melanoma. Current Problems In Cancer 2011, 35: 211-224. PMID: 21911184, DOI: 10.1016/j.currproblcancer.2011.07.004.Peer-Reviewed Original Research
2010
Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032
Rubinstein JC, Sznol M, Pavlick AC, Ariyan S, Cheng E, Bacchiocchi A, Kluger HM, Narayan D, Halaban R. Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. Journal Of Translational Medicine 2010, 8: 67. PMID: 20630094, PMCID: PMC2917408, DOI: 10.1186/1479-5876-8-67.Peer-Reviewed Original ResearchConceptsV600K mutationsClinical trialsBRAF V600E/K mutationK mutationPotential therapeutic responseMutant BRAF inhibitorsBRAF inhibitor PLX4032BRAF V600K mutationMelanoma patientsTherapeutic responseBRAF mutationsPatientsV600E mutationInhibitor PLX4032BRAF kinasePLX4032TrialsCommon mutationsMutationsMelanomaIncidence