2016
RASopathy Gene Mutations in Melanoma
Halaban R, Krauthammer M. RASopathy Gene Mutations in Melanoma. Journal Of Investigative Dermatology 2016, 136: 1755-1759. PMID: 27236105, PMCID: PMC4992636, DOI: 10.1016/j.jid.2016.05.095.Peer-Reviewed Original ResearchConceptsRASopathy mutationsRAS/mitogen-activated protein kinaseRAS/mitogen-activated protein kinase (MAPK) pathwayMitogen-activated protein kinase pathwayMitogen-activated protein kinaseProtein kinase pathwayAmino acid substitutionsNext-generation sequencingProtein kinasePathway genesKinase pathwaySequencing dataDriver genesAcid substitutionsGenomic abnormalitiesMutationsLegius syndromeGenesAbundant mutationsGermline mutationsGene mutationsPathwaySignificant overlapKinaseMelanomagenesis
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, CulturedGenomic Classification of Cutaneous Melanoma
Network T, Akbani R, Akdemir K, Aksoy B, Albert M, Ally A, Amin S, Arachchi H, Arora A, Auman J, Ayala B, Baboud J, Balasundaram M, Balu S, Barnabas N, Bartlett J, Bartlett P, Bastian B, Baylin S, Behera M, Belyaev D, Benz C, Bernard B, Beroukhim R, Bir N, Black A, Bodenheimer T, Boice L, Boland G, Bono R, Bootwalla M, Bosenberg M, Bowen J, Bowlby R, Bristow C, Brockway-Lunardi L, Brooks D, Brzezinski J, Bshara W, Buda E, Burns W, Butterfield Y, Button M, Calderone T, Cappellini G, Carter C, Carter S, Cherney L, Cherniack A, Chevalier A, Chin L, Cho J, Cho R, Choi Y, Chu A, Chudamani S, Cibulskis K, Ciriello G, Clarke A, Coons S, Cope L, Crain D, Curley E, Danilova L, D’Atri S, Davidsen T, Davies M, Delman K, Demchok J, Deng Q, Deribe Y, Dhalla N, Dhir R, DiCara D, Dinikin M, Dubina M, Ebrom J, Egea S, Eley G, Engel J, Eschbacher J, Fedosenko K, Felau I, Fennell T, Ferguson M, Fisher S, Flaherty K, Frazer S, Frick J, Fulidou V, Gabriel S, Gao J, Gardner J, Garraway L, Gastier-Foster J, Gaudioso C, Gehlenborg N, Genovese G, Gerken M, Gershenwald J, Getz G, Gomez-Fernandez C, Gribbin T, Grimsby J, Gross B, Guin R, Gutschner T, Hadjipanayis A, Halaban R, Hanf B, Haussler D, Haydu L, Hayes D, Hayward N, Heiman D, Herbert L, Herman J, Hersey P, Hoadley K, Hodis E, Holt R, Hoon D, Hoppough S, Hoyle A, Huang F, Huang M, Huang S, Hutter C, Ibbs M, Iype L, Jacobsen A, Jakrot V, Janning A, Jeck W, Jefferys S, Jensen M, Jones C, Jones S, Ju Z, Kakavand H, Kang H, Kefford R, Khuri F, Kim J, Kirkwood J, Klode J, Korkut A, Korski K, Krauthammer M, Kucherlapati R, Kwong L, Kycler W, Ladanyi M, Lai P, Laird P, Lander E, Lawrence M, Lazar A, Łaźniak R, Lee D, Lee J, Lee J, Lee K, Lee S, Lee W, Leporowska E, Leraas K, Li H, Lichtenberg T, Lichtenstein L, Lin P, Ling S, Liu J, Liu O, Liu W, Long G, Lu Y, Ma, Ma Y, Mackiewicz A, Mahadeshwar H, Malke J, Mallery D, Manikhas G, Mann G, Marra M, Matejka B, Mayo M, Mehrabi S, Meng S, Meyerson M, Mieczkowski P, Miller J, Miller M, Mills G, Moiseenko F, Moore R, Morris S, Morrison C, Morton D, Moschos S, Mose L, Muller F, Mungall A, Murawa D, Murawa P, Murray B, Nezi L, Ng S, Nicholson D, Noble M, Osunkoya A, Owonikoko T, Ozenberger B, Pagani E, Paklina O, Pantazi A, Parfenov M, Parfitt J, Park P, Park W, Parker J, Passarelli F, Penny R, Perou C, Pihl T, Potapova O, Prieto V, Protopopov A, Quinn M, Radenbaugh A, Rai K, Ramalingam S, Raman A, Ramirez N, Ramirez R, Rao U, Rathmell W, Ren X, Reynolds S, Roach J, Robertson A, Ross M, Roszik J, Russo G, Saksena G, Saller C, Samuels Y, Sander C, Sander C, Sandusky G, Santoso N, Saul M, Saw R, Schadendorf D, Schein J, Schultz N, Schumacher S, Schwallier C, Scolyer R, Seidman J, Sekhar P, Sekhon H, Senbabaoglu Y, Seth S, Shannon K, Sharpe S, Sharpless N, Shaw K, Shelton C, Shelton T, Shen R, Sheth M, Shi Y, Shiau C, Shmulevich I, Sica G, Simons J, Sinha R, Sipahimalani P, Sofia H, Soloway M, Song X, Sougnez C, Spillane A, Spychała A, Stretch J, Stuart J, Suchorska W, Sucker A, Sumer S, Sun Y, Synott M, Tabak B, Tabler T, Tam A, Tan D, Tang J, Tarnuzzer R, Tarvin K, Tatka H, Taylor B, Teresiak M, Thiessen N, Thompson J, Thorne L, Thorsson V, Trent J, Triche T, Tsai K, Tsou P, Van Den Berg D, Van Allen E, Veluvolu U, Verhaak R, Voet D, Voronina O, Walter V, Walton J, Wan Y, Wang Y, Wang Z, Waring S, Watson I, Weinhold N, Weinstein J, Weisenberger D, White P, Wilkerson M, Wilmott J, Wise L, Wiznerowicz M, Woodman S, Wu C, Wu C, Wu J, Wu Y, Xi R, Xu A, Yang D, Yang L, Yang L, Zack T, Zenklusen J, Zhang H, Zhang J, Zhang W, Zhao X, Zhu J, Zhu K, Zimmer L, Zmuda E, Zou L. Genomic Classification of Cutaneous Melanoma. Cell 2015, 161: 1681-1696. PMID: 26091043, PMCID: PMC4580370, DOI: 10.1016/j.cell.2015.05.044.Peer-Reviewed Original ResearchConceptsGenomic classificationProtein-based analysesComplex structural rearrangementsImmune gene expressionMutant RASGene expressionIntegrative analysisFocal amplificationGenomic alterationsStructural rearrangementsProtein expressionMutant BRAFCell markersExpressionGenesRNADNAMutationsCutaneous melanomaKIT mutationsNF1RASRearrangementEnrichmentLandscape
2014
RAC1 and Melanoma
Halaban R. RAC1 and Melanoma. Clinical Therapeutics 2014, 37: 682-685. PMID: 25465943, PMCID: PMC4415501, DOI: 10.1016/j.clinthera.2014.10.027.Peer-Reviewed Original ResearchRare SF3B1 R625 mutations in cutaneous melanoma
Kong Y, Krauthammer M, Halaban R. Rare SF3B1 R625 mutations in cutaneous melanoma. Melanoma Research 2014, 24: 332-334. PMID: 24709888, PMCID: PMC4101881, DOI: 10.1097/cmr.0000000000000071.Peer-Reviewed Original ResearchIdentification of PLX4032‐resistance mechanisms and implications for novel RAF inhibitors
Choi J, Landrette SF, Wang T, Evans P, Bacchiocchi A, Bjornson R, Cheng E, Stiegler AL, Gathiaka S, Acevedo O, Boggon TJ, Krauthammer M, Halaban R, Xu T. Identification of PLX4032‐resistance mechanisms and implications for novel RAF inhibitors. Pigment Cell & Melanoma Research 2014, 27: 253-262. PMID: 24283590, PMCID: PMC4065135, DOI: 10.1111/pcmr.12197.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell Line, TumorCell ProliferationDNA Transposable ElementsDrug Resistance, NeoplasmHumansIndolesMAP Kinase Signaling SystemMelanomaModels, MolecularMolecular Sequence DataMutagenesis, InsertionalMutant ProteinsMutationProtein Kinase InhibitorsProto-Oncogene Proteins B-rafSulfonamidesVemurafenibConceptsBRAF mutationsNovel BRAF mutationBRAF inhibitorsNext-generation BRAF inhibitorsPLX4032-resistant melanoma cellsMelanoma cellsMelanoma patient survivalHuman prostate cancerBRAF mutant cellsWhole-exome sequencingMelanoma patientsPatient survivalClinical trialsProstate cancerRAF inhibitorsOncogenic mutationsNew screening approachRelevant aberrationsInhibitorsCellsMutationsScreening approachNovel RAF inhibitorsPatientsPLX8394
2012
Preexisting 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
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
2002
Coexpression of Wild-Type Tyrosinase Enhances Maturation of Temperature-Sensitive Tyrosinase Mutants
Halaban R, Cheng E, Hebert DN. Coexpression of Wild-Type Tyrosinase Enhances Maturation of Temperature-Sensitive Tyrosinase Mutants. Journal Of Investigative Dermatology 2002, 119: 481-488. PMID: 12190874, DOI: 10.1046/j.1523-1747.2002.01824.x.Peer-Reviewed Original ResearchConceptsWild-type proteinTyrosinase mutantsMutant proteinsGlycosylation-deficient mutantsGlycosylation-deficient formsOculocutaneous albinism 1Wild-type tyrosinaseDevelopment of pigmentsDifferent mutant allelesType I membraneActivity-dependent mannerNonpermissive temperatureMutant allelesEndoplasmic reticulumTypes of mutationsMutantsFunction mutationsCarbohydrate processingMelanin synthesisProteinCoexpressionMelanocytesTyrosinase activityMutationsMaturation
1998
Identification of morc (microrchidia), a mutation that results in arrest of spermatogenesis at an early meiotic stage in the mouse
Watson M, Zinn A, Inoue N, Hess K, Cobb J, Handel M, Halaban R, Duchene C, Albright G, Moreadith R. Identification of morc (microrchidia), a mutation that results in arrest of spermatogenesis at an early meiotic stage in the mouse. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 14361-14366. PMID: 9826705, PMCID: PMC24378, DOI: 10.1073/pnas.95.24.14361.Peer-Reviewed Original ResearchConceptsMammalian germ cell developmentGerm cellsGerm cell developmentNovel biochemical pathwaysEarly meiotic stagesTransgene expressionMale gametogenesisMouse strain transgenicGenomic analysisProphase IMutant animalsTransgene insertionCDNA constructsEye pigmentationBiochemical pathwaysLeptotene stageAbnormal phenotypeCell developmentMeiotic stagesMeiosisMutation resultsArrest of spermatogenesisGenesSpermatogenesisMutations
1994
Characterization of Mouse Pmel 17 Gene and Silver Locus
KWON B, KIM K, HALABAN R, PICKARD R. Characterization of Mouse Pmel 17 Gene and Silver Locus. Pigment Cell & Melanoma Research 1994, 7: 394-397. PMID: 7761347, DOI: 10.1111/j.1600-0749.1994.tb00067.x.Peer-Reviewed Original ResearchConceptsCDNA clonesPutative cytoplasmic tailPmel 17Amino acidsC-terminal amino acidsSingle nucleotide insertionSilver locusGenomic regionsCytoplasmic tailCarboxyl terminusC-terminusMurine melanocytesNucleotide insertionMutation sitesProteinClonesGenesTerminusLociMajor defectsMutationsResiduesAcidMelanocytesInsertion
1990
Murine and human b locus pigmentation genes encode a glycoprotein (gp75) with catalase activity.
Halaban R, Moellmann G. Murine and human b locus pigmentation genes encode a glycoprotein (gp75) with catalase activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 1990, 87: 4809-4813. PMID: 1693779, PMCID: PMC54207, DOI: 10.1073/pnas.87.12.4809.Peer-Reviewed Original ResearchConceptsPigmentation genesRapid proteolytic degradationMelanosomal glycoproteinLocus proteinBrown locusCatalase BB mutationsProteolytic degradationB locusMelanogenic activityGenesMelanin precursorsLociProteinMutationsGlycoproteinCatalase activityTyrosinaseHydrogen peroxideHydroperoxidaseMelanogenesisGp75ActivityMurinePigmentation
1989
Molecular basis of mouse Himalayan mutation
Kwon B, Halaban R, Chintamaneni C. Molecular basis of mouse Himalayan mutation. Biochemical And Biophysical Research Communications 1989, 161: 252-260. PMID: 2567165, DOI: 10.1016/0006-291x(89)91588-x.Peer-Reviewed Original ResearchConceptsAmino acid 420Histidine residuesAmino acidsTemperature-sensitive tyrosinaseCDNA libraryHimalayan miceMouse tyrosinaseInteresting mutantsNucleotide sequenceB proteinMolecular basisTyrosinase geneTyrosinase cDNAArginine residuesTyrosinase moleculesHuman tyrosinaseG changeResiduesMutationsTyrosinaseMutantsCDNAGenesMiceTyrosinase inhibitors
1988
Tyrosinases of murine melanocytes with mutations at the albino locus.
Halaban R, Moellmann G, Tamura A, Kwon BS, Kuklinska E, Pomerantz SH, Lerner AB. Tyrosinases of murine melanocytes with mutations at the albino locus. Proceedings Of The National Academy Of Sciences Of The United States Of America 1988, 85: 7241-7245. PMID: 3140237, PMCID: PMC282161, DOI: 10.1073/pnas.85.19.7241.Peer-Reviewed Original ResearchConceptsAlbino locusTrans-Golgi networkWild-type melanocytesWild-type strainAbnormal posttranslational modificationsSynthesis of melaninDiminished pigmentationStructural genePosttranslational modificationsMurine melanocytesLocus mutantsKey enzymeLevels of mRNAMutantsKinetics of activationProteolytic cleavageUnstable enzymeEnzymeLociMelanocytesReduced levelsMutationsConfer susceptibilityTyrosinaseLittle enzyme