2019
Genomic sites hypersensitive to ultraviolet radiation
Premi S, Han L, Mehta S, Knight J, Zhao D, Palmatier MA, Kornacker K, Brash DE. Genomic sites hypersensitive to ultraviolet radiation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 24196-24205. PMID: 31723047, PMCID: PMC6883822, DOI: 10.1073/pnas.1907860116.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated RegionsCells, CulturedDNA DamageFibroblastsGene Expression RegulationGenome, HumanHigh-Throughput Nucleotide SequencingHumansMelanocytesMelanomaMutationPromoter Regions, GeneticProtein BiosynthesisPyrimidine DimersPyrimidine NucleotidesSkin NeoplasmsTOR Serine-Threonine KinasesUltraviolet RaysConceptsCyclobutane pyrimidine dimersETS family transcription factorsIndividual gene promotersFamily transcription factorsRNA-binding proteinPrimary human melanocytesSingle-base resolutionEpigenetic marksGenomic averageTranslation regulationGenomic sitesMotif locationsTranscription factorsCell physiologyGene promoterCancer driversGenomeHuman melanocytesCell typesTumor evolutionCell pathwaysRare mutationsUV targetPyrimidine dimersApurinic sitesAccelerating cancer without mutations
Brash DE. Accelerating cancer without mutations. ELife 2019, 8: e45809. PMID: 30895924, PMCID: PMC6428566, DOI: 10.7554/elife.45809.Commentaries, Editorials and Letters
2016
Chemical excitation of electrons: A dark path to melanoma
Premi S, Brash DE. Chemical excitation of electrons: A dark path to melanoma. DNA Repair 2016, 44: 169-177. PMID: 27262612, PMCID: PMC4958542, DOI: 10.1016/j.dnarep.2016.05.023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2015
Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure
Premi S, Wallisch S, Mano CM, Weiner AB, Bacchiocchi A, Wakamatsu K, Bechara EJ, Halaban R, Douki T, Brash DE. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science 2015, 347: 842-847. PMID: 25700512, PMCID: PMC4432913, DOI: 10.1126/science.1256022.Peer-Reviewed Original ResearchConceptsDark cyclobutane pyrimidine dimersExcited electronic statesUltraviolet photonsUV photonsElectronic statesTriplet stateSunlight-induced melanomaCytosine-containing cyclobutane pyrimidine dimersEnergy transferPhotonsPicosecondsElectronsUV exposureRadiationChemiexcitationEnergyStatePhotoproducts
2012
Exome 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 melanomas
2009
Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia
Klein AM, Brash DE, Jones PH, Simons BD. Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 107: 270-275. PMID: 20018764, PMCID: PMC2806764, DOI: 10.1073/pnas.0909738107.Peer-Reviewed Original ResearchConceptsP53 mutationsNonmelanoma skin cancer incidenceSame cumulative doseSkin cancer incidenceUVB radiationUV-irradiated epidermisP53 tumor suppressor geneP53-mutant clonesCumulative doseCancer incidenceP53 mutant cellsHigh-intensity exposureMurine epidermisPreneoplastic clonesTumor suppressor geneProgenitor cellsExposure resultsPrecancerous cellsPreneoplastic cellsHuman epidermisB radiationClones of cells
2008
Preneoplastic lesion growth driven by the death of adjacent normal stem cells
Chao DL, Eck JT, Brash DE, Maley CC, Luebeck EG. Preneoplastic lesion growth driven by the death of adjacent normal stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 15034-15039. PMID: 18815380, PMCID: PMC2567488, DOI: 10.1073/pnas.0802211105.Peer-Reviewed Original ResearchConceptsNormal stem cellsStem cellsClonal expansionCell replicationMutant cellsNormal cell replicationMutant clonesProliferative advantageDorsal epidermisCell mutationTissue architectureClonesClone growthBiological observationsCell killingApoptosis rateReplicationMutationsGrowth rateCellsGrowthNormal territoriesApoptosisExponential growth modelImportant step
2006
Keratinocyte Apoptosis in Epidermal Development and Disease
Raj D, Brash DE, Grossman D. Keratinocyte Apoptosis in Epidermal Development and Disease. Journal Of Investigative Dermatology 2006, 126: 243-257. PMID: 16418733, PMCID: PMC2291295, DOI: 10.1038/sj.jid.5700008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEpidermal developmentNormal developmental programPre-malignant cellsDevelopmental programApoptosis controlMolecular mechanismsKeratinocyte apoptosisDysfunctional apoptosisKC apoptosisApoptosisCritical roleComplex roleNew insightsCorneum formationMouse modelCarcinogenesisSkin carcinogenesisPathwayRoleProliferationCells
2005
PTCH codon 1315 polymorphism and risk for nonmelanoma skin cancer
Asplund A, Gustafsson AC, Wikonkal NM, Sela A, Leffell DJ, Kidd K, Lundeberg J, Brash DE, Pontén F. PTCH codon 1315 polymorphism and risk for nonmelanoma skin cancer. British Journal Of Dermatology 2005, 152: 868-873. PMID: 15888139, DOI: 10.1111/j.1365-2133.2005.06464.x.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Basal CellCarcinoma, Squamous CellCodonGenetic Predisposition to DiseaseGenotypeHair ColorHumansLoss of HeterozygosityNeoplasm ProteinsPatched ReceptorsPatched-1 ReceptorPilot ProjectsPolymerase Chain ReactionPolymorphism, Single NucleotideReceptors, Cell SurfaceSkin NeoplasmsSkin PigmentationConceptsPro/Pro genotypeNonmelanoma skin cancerBasal cell carcinomaPTCH tumor suppressor geneSquamous cell carcinomaAllele frequency variationAllelic loss studiesTumor suppressor genePro genotypeSingle nucleotide polymorphismsAllelic lossGenomic DNANonrandom lossSuppressor geneCell carcinomaSwedish patientsEpithelial cell cancersLight pigmentationSkin cancerNucleotide polymorphismsMultiple basal cell carcinomasPro/LeuHuman populationPTCH geneAllele frequenciesColonization of adjacent stem cell compartments by mutant keratinocytes
Brash DE, Zhang W, Grossman D, Takeuchi S. Colonization of adjacent stem cell compartments by mutant keratinocytes. Seminars In Cancer Biology 2005, 15: 97-102. PMID: 15652454, DOI: 10.1016/j.semcancer.2004.08.006.ChaptersMeSH KeywordsAnimalsApoptosisKeratinocytesMutagenesisSkin NeoplasmsStem CellsTumor Suppressor Protein p53Ultraviolet RaysConceptsStem cell compartmentMutant stem cellsCell compartmentStem cellsDNA-damaged cellsNon-mutational mechanismsMutant cellsAdditional genesClonal expansionSelection pressureP53 mutant cellsUVB-induced apoptosisMutant keratinocytesCancer developmentCompartmentsCellsAbsence of escapeKeratinocyte clonesAdditional territoryClinical phenotypeAdjacent compartmentsGenesMechanismClonesPhenotype
2004
Melanin acts as a potent UVB photosensitizer to cause an atypical mode of cell death in murine skin
Takeuchi S, Zhang W, Wakamatsu K, Ito S, Hearing VJ, Kraemer KH, Brash DE. Melanin acts as a potent UVB photosensitizer to cause an atypical mode of cell death in murine skin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 15076-15081. PMID: 15477596, PMCID: PMC524044, DOI: 10.1073/pnas.0403994101.Peer-Reviewed Original ResearchConceptsYellow miceTerminal deoxynucleotidyltransferase-mediated dUTP nickTUNEL-positive cellsActive caspase-3Sunburn cellsPositive cellsBlack miceSkin cancerCongenic miceMurine skinDUTP nickDNA strand breaksMiceEpidermal sheetsHair folliclesAbility of melaninCaspase-3Sensitivity of individualsApoptosisLesionsUVA radiationRed hairCell deathHair shaftSunlight UV radiationUVB-induced apoptosis drives clonal expansion during skin tumor development
Zhang W, Hanks AN, Boucher K, Florell SR, Allen SM, Alexander A, Brash DE, Grossman D. UVB-induced apoptosis drives clonal expansion during skin tumor development. Carcinogenesis 2004, 26: 249-257. PMID: 15498793, PMCID: PMC2292404, DOI: 10.1093/carcin/bgh300.Peer-Reviewed Original Research
2003
Photocopying Cancer Cells
Brash DE. Photocopying Cancer Cells. Journal Of Investigative Dermatology 2003, 121: xiii-xiv. PMID: 12839596, DOI: 10.1046/j.1523-1747.2003.12381.x.Commentaries, Editorials and LettersInactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice
Wikonkal NM, Remenyik E, Knezevic D, Zhang W, Liu M, Zhao H, Berton TR, Johnson DG, Brash DE. Inactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice. Nature Cell Biology 2003, 5: 655-660. PMID: 12833065, DOI: 10.1038/ncb1001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Cycle ProteinsCell SurvivalCell Transformation, NeoplasticCells, CulturedDNA DamageDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorFemaleFibroblastsGene Expression Regulation, NeoplasticGenes, SuppressorKeratinocytesMaleMiceMice, KnockoutMutationSex RatioSkin NeoplasmsTranscription FactorsTumor Suppressor Protein p53Ultraviolet RaysConceptsUVB-induced apoptosisEarly-onset tumorsDouble knockout miceTrp53-deficient miceKnockout miceCancer sensitivityUVB exposureGenetic abnormalitiesMiceKeratinocyte apoptosisProtective mechanismApoptosis defectsApoptosis resistanceApoptosisDouble knockoutApoptosis pathwayE2F1 transcription factorE2F1 functionsPrimary fibroblastsE2F1Trp53S phase
1999
Induction of cyclin-dependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine
Liu M, Wikonkal N, Brash D. Induction of cyclin-dependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine. Carcinogenesis 1999, 20: 1869-1872. PMID: 10469636, DOI: 10.1093/carcin/20.9.1869.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsAnticarcinogenic AgentsAntioxidantsCell CycleCell LineChromansCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21CyclinsFibroblastsFree Radical ScavengersG1 PhaseGene Expression RegulationGene Expression Regulation, NeoplasticGenes, p16GlutathioneHumansKeratinocytesMiceModels, BiologicalNeoplasm ProteinsPapillomaSkin NeoplasmsTumor Cells, CulturedTumor Suppressor Protein p53ConceptsCyclin-dependent kinase inhibitorNovel molecular basisCell cycle transitionKinase inhibitorsDNA replicationDNA repairCellular differentiationMolecular basisG1 prolongationGene expressionAntioxidant N-acetylcysteineN-acetylcysteineIntracellular glutathione levelsArrestAgent N-acetylcysteineInductionInhibitorsGlutathione levelsCyclinChemopreventive agentsChemopreventive activityDifferentiationUsual mechanismP53ReplicationUltraviolet Radiation Induced Signature Mutations in Photocarcinogenesis
Wikonkal N, Brash D. Ultraviolet Radiation Induced Signature Mutations in Photocarcinogenesis. Journal Of Investigative Dermatology Symposium Proceedings 1999, 4: 6-10. PMID: 10537000, DOI: 10.1038/sj.jidsp.5640173.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSignature mutationsSkin cancerNon-melanoma skin cancerUV-signature mutationsClinical dataSubstantial burdenSkin carcinogenesisMurine epidermisNormal individualsNormal humansCancerCancer developmentTumor suppressor geneClonal expansionTumor promoterTP53Suppressor geneGenetic eventsMutationsCells
1998
Skin precancer.
Brash DE, Pontén J. Skin precancer. Cancer Surveys 1998, 32: 69-113. PMID: 10489624.ChaptersConceptsTP53 mutationsClonal expansionCell carcinomaHair follicle originHigh-risk papillomasRegression of dysplasiaTP53 mutant clonesSquamous cell carcinomaBasal cell carcinomaRegression of melanomaCell of originPrecancerous eventsBCC tumorsMelanoma cell linesGenetics of melanomaPrecancerous lesionsRelative riskFamilial predispositionSuch lesionsImmunosuppressant drugsDysplastic naeviNormal skinPrecancerChemotherapeutic agentsMelanoma
1997
Sunlight and the onset of skin cancer
Brash D. Sunlight and the onset of skin cancer. Trends In Genetics 1997, 13: 410-414. PMID: 9351343, DOI: 10.1016/s0168-9525(97)01246-8.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
1996
The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas
Gailani M, Ståhle-Bäckdahl M, Leffell D, Glyn M, Zaphiropoulos P, Undén A, Dean M, Brash D, Bale A, Toftgård R. The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nature Genetics 1996, 14: 78-81. PMID: 8782823, DOI: 10.1038/ng0996-78.Peer-Reviewed Original ResearchConceptsSporadic basal cell carcinomasSingle-strand conformational polymorphismTumor suppressorDrosophila segment polarity geneSegment polarity genesHedgehog target genesPolarity genesDrosophila mutantsStrong homologyHuman homologueTarget genesMutational inactivationMutant transcriptsStrand conformational polymorphismNorthern blotSSCP variantsGenesNegative feedback mechanismSitu hybridizationConformational polymorphismNevoid basal cell carcinoma syndromeSuppressorAllelic lossInactivationMutationsSunlight and skin cancer.
Leffell DJ, Brash DE. Sunlight and skin cancer. Scientific American 1996, 275: 52-3, 56-9. PMID: 8658110, DOI: 10.1038/scientificamerican0796-52.Publications for non-academic audiences