2022
Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis
Farshidfar F, Rhrissorrakrai K, Levovitz C, Peng C, Knight J, Bacchiocchi A, Su J, Yin M, Sznol M, Ariyan S, Clune J, Olino K, Parida L, Nikolaus J, Zhang M, Zhao S, Wang Y, Huang G, Wan M, Li X, Cao J, Yan Q, Chen X, Newman AM, Halaban R. Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis. Nature Communications 2022, 13: 898. PMID: 35197475, PMCID: PMC8866401, DOI: 10.1038/s41467-022-28566-4.Peer-Reviewed Original ResearchConceptsAcral melanomaMelanoma subtypesClinical profilingCommon melanoma subtypeImmune checkpoint blockadeCheckpoint blockadeInferior survivalMelanoma cell linesKey molecular driversPoor prognosisTherapeutic targetAnchorage-independent growthImmunomodulatory genesNon-white individualsHotspot mutationsMolecular driversCandidate oncogeneMelanomaApoptotic cell deathLZTR1Focal amplificationTumor promoterCell linesMetastasisTumor suppressor
2019
A novel anti-melanoma SRC-family kinase inhibitor
Halaban R, Bacchiocchi A, Straub R, Cao J, Sznol M, Narayan D, Allam A, Krauthammer M, Mansour TS. A novel anti-melanoma SRC-family kinase inhibitor. Oncotarget 2019, 10: 2237-2251. PMID: 31040916, PMCID: PMC6481345, DOI: 10.18632/oncotarget.26787.Peer-Reviewed Original ResearchSrc family kinase inhibitorMAPK inhibitorTranscription factor MITFPatient-derived melanoma cellsPI3K activityKinase inhibitorsSynergistic growth inhibitionGrowth arrestMelanoma cell linesK activityProteolytic degradationCell linesERBB2 inhibitionOncogene expressionMelanoma therapyTumor growthDrug resistanceMelanoma cellsGrowth inhibitionAlternative targetsActivity leadInhibitorsPP2ASHP2Inhibition
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 associationPreexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors
Shi H, Moriceau G, Kong X, Koya RC, Nazarian R, Pupo GM, Bacchiocchi A, Dahlman KB, Chmielowski B, Sosman JA, Halaban R, Kefford RF, Long GV, Ribas A, Lo RS. Preexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors. Cancer Discovery 2012, 2: 414-424. PMID: 22588879, PMCID: PMC3594852, DOI: 10.1158/2159-8290.cd-12-0022.Peer-Reviewed Original ResearchConceptsBRAF inhibitorsActivating mutationsObjective tumor responseMEK1/2 inhibitorMEK1 mutationsP-ERK1/2 levelsBRAF-mutant melanomaMelanoma cell linesAdvanced melanomaAntitumor responseExon 3 mutationsTumor responseDisease progressionMelanomaBRAFi resistanceDrug sensitivitySignificant alterationsPatientsCell linesInhibitorsBaselineMutationsExon 3Widespread use
1997
Regulation of fibroblast growth factor 2 expression in melanoma cells by the c-MYB proto-oncoprotein.
Miglarese M, Halaban R, Gibson N. Regulation of fibroblast growth factor 2 expression in melanoma cells by the c-MYB proto-oncoprotein. Molecular Cancer Research 1997, 8: 1199-210. PMID: 9372243.Peer-Reviewed Original ResearchConceptsFGF-2 promoterMurine c-MybSK-MEL-2 human melanoma cellsC-MybFunctional DNA-binding domainHuman melanoma cellsDNA-binding domainMelanoma cellsAutocrine growthPutative MybC-myb mRNATranscription factorsEctopic expressionPromoter regionFibroblast growth factorBasic fibroblast growth factorMelanoma cell linesReporter plasmidNormal melanocytesFibroblast growth factor-2 expressionPromoterGrowth factor 2 expressionMYBFGF-2 proteinCell linesAberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells
Halaban R, Cheng E, Zhang Y, Moellmann G, Hanlon D, Michalak M, Setaluri V, Hebert D. Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 6210-6215. PMID: 9177196, PMCID: PMC21028, DOI: 10.1073/pnas.94.12.6210.Peer-Reviewed Original ResearchMeSH KeywordsAdultCalcium-Binding ProteinsCalnexinCalreticulinCell DifferentiationCells, CulturedCoculture TechniquesEndoplasmic ReticulumEnzyme PrecursorsHumansInfant, NewbornKineticsMelanocytesMelanomaMolecular ChaperonesMolecular WeightMonophenol MonooxygenasePhenotypeRibonucleoproteinsSkin NeoplasmsTime FactorsTumor Cells, CulturedConceptsEndoplasmic reticulumNormal melanocytesER chaperone calnexinMelanin synthesisMalignant melanocytesMelanoma cellsChaperone bindingAberrant retentionChaperone calnexinGolgi compartmentSubcellular localizationAmelanotic melanoma cell lineKey enzymeMelanoma cell linesMaturation of tyrosinaseAmelanotic melanoma cellsKinetics of synthesisInhibitor sensitivityDedifferentiated phenotypeProteolytic degradationCell linesProteasome inhibitorsEnzymeProteasomeImmature forms
1993
KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells.
Zakut R, Perlis R, Eliyahu S, Yarden Y, Givol D, Lyman S, Halaban R. KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells. Oncogene 1993, 8: 2221-9. PMID: 7687762.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell DivisionHematopoietic Cell Growth FactorsHumansMelanomaMolecular Sequence DataNeoplasm ProteinsPhosphorylationProtein-Tyrosine KinasesProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins c-kitRNA, MessengerRNA, NeoplasmStem Cell FactorTumor Cells, CulturedConceptsMast cell growth factorMelanoma cell linesNormal melanocyte developmentMelanoma cellsAberrant signal transductionMetastatic melanoma cell linesCell linesActivation of KITMelanocyte developmentSignal transductionKIT proto-oncogeneKinase activationKIT mRNAKit ligandNormal melanocytesProto-oncogeneKIT kinaseCell growth factorBiological responsesGrowth factorHuman melanomaMelanocytesCellsKIT expressionNeoplastic melanocytes
1989
Isolation, Chromosomal Mapping, and Expression of the Mouse Tyrosinase Gene
Kwon B, Haq A, Wakulchik M, Kestler D, Barton D, Francke U, Lamoreux M, Whitney J, Halaban R. Isolation, Chromosomal Mapping, and Expression of the Mouse Tyrosinase Gene. Journal Of Investigative Dermatology 1989, 93: 589-594. PMID: 2507645, DOI: 10.1111/1523-1747.ep12319693.Peer-Reviewed Original ResearchConceptsMouse tyrosinaseTyrosinase geneMouse chromosome 7Mouse tyrosinase geneSomatic cell hybridsSouthern blot analysisChromosomal mappingGenomic clonesCell hybridsPromoter sequencesTATA elementAlbino locusChromosome 7Melanoma cell linesCDNA probeNormal melanocytesTyrosinase mRNABackcross miceBlot analysisFarthest upstreamCell linesDeletion miceGenesLociCloudman S
1986
Human Melanocytes Cultured from Nevi and Melanomas
Halaban R, Ghosh S, Duray P, Kirkwood J, Lerner A. Human Melanocytes Cultured from Nevi and Melanomas. Journal Of Investigative Dermatology 1986, 87: 95-101. PMID: 2425008, DOI: 10.1111/1523-1747.ep12523594.Peer-Reviewed Original ResearchConceptsPresence of mitogensHuman melanocytesNeonatal melanocytesRate of proliferationPrimary melanomaCongenital neviMalignant transformationTransformation of melanocytesCholera toxinIsobutylmethyl xanthineHuman placentaGrowth factorProliferative rateMelanomaNewborn foreskinUnidentified factorsCell linesMelanocytesMitogenNeviHuman neonatal melanocytesPopulation doublingsMonthsLate eventProliferation
1985
Primary Melanoma Cells of the Vertical Growth Phase: Similarities to Metastatic Cells2
Herlyn M, Balaban G, Bennicelli J, Guerry D, Halaban R, Herlyn D, Elder D, Maul G, Steplewski Z, Nowell P, Clark W, Koprowski H. Primary Melanoma Cells of the Vertical Growth Phase: Similarities to Metastatic Cells2. Journal Of The National Cancer Institute 1985, 74: 283-289. PMID: 3856042, DOI: 10.1093/jnci/74.2.283.Peer-Reviewed Original ResearchConceptsVertical growth phaseMetastatic melanoma cellsMelanoma cellsMetastatic lesionsPrimary melanomaMetastatic cellsMelanoma-associated antigensMixed hemadsorption assaysPrimary melanoma cellsLong-term cultured cellsMetastatic melanoma cell linesGrowth phaseMelanoma cell linesRadial growth phaseMalignant melanomaNude micePopulation-doubling timeNonrandom abnormalitiesFlow cytometryHemadsorption assaysMonoclonal antibodiesMelanomaPatientsCell linesLesions