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
2010
Human Telomeres Are Hypersensitive to UV-Induced DNA Damage and Refractory to Repair
Rochette PJ, Brash DE. Human Telomeres Are Hypersensitive to UV-Induced DNA Damage and Refractory to Repair. PLOS Genetics 2010, 6: e1000926. PMID: 20442874, PMCID: PMC2861706, DOI: 10.1371/journal.pgen.1000926.Peer-Reviewed Original ResearchConceptsUV-induced DNA damageDNA damageTelomeric repeatsHuman telomeresExcision repairTelomeric repeat unitsNucleotide excision repairDouble-strand breaksUV-induced CPDGenome integrityGenomic integrityExcision repair sitesMitochondrial DNARegion of p53Opposite strandTelomeresCPD removalUnrepaired lesionsRepeatsPreeminent risk factorUV sensitivityPyrimidine dimersCancer developmentRepeat unitsCritical role
2009
Influence of cytosine methylation on ultraviolet-induced cyclobutane pyrimidine dimer formation in genomic DNA
Rochette PJ, Lacoste S, Therrien JP, Bastien N, Brash DE, Drouin R. Influence of cytosine methylation on ultraviolet-induced cyclobutane pyrimidine dimer formation in genomic DNA. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis 2009, 665: 7-13. PMID: 19427505, DOI: 10.1016/j.mrfmmm.2009.02.008.Peer-Reviewed Original ResearchConceptsLigation-mediated PCRX chromosomeFMR1 geneGenomic DNAInactive X chromosomeDimer formationCyclobutane pyrimidine dimer formationTumor suppressor genePyrimidine dimer formationConstitutive methylationCytosine methylationMethylated cytosineUnmethylated cytosinesSuppressor geneP53 tumor suppressor geneGenesMethylationCPD formationChromosomesCytosineDNAMutationsSunlight-induced mutationsDipyrimidine sitesPGK1
2008
Progressive apoptosis resistance prior to senescence and control by the anti-apoptotic protein BCL-xL
Rochette PJ, Brash DE. Progressive apoptosis resistance prior to senescence and control by the anti-apoptotic protein BCL-xL. Mechanisms Of Ageing And Development 2008, 129: 207-214. PMID: 18262222, PMCID: PMC2652169, DOI: 10.1016/j.mad.2007.12.007.Peer-Reviewed Original ResearchConceptsAnti-apoptotic protein Bcl-xLBcl-xLProtein Bcl-xLLevels of p53Pro-apoptotic protein BaxApoptosis reductionAnti-apoptotic proteinsPro-apoptotic BaxNormal balanceAnti-apoptotic Bcl-xLUV-induced apoptosisOld cellsApoptosis resistanceProgressive disruptionSenescent cellsApoptosisBaxProtein BaxHuman diploid fibroblastsCellsYoung cellsDiploid fibroblastsGenotoxic stressLevels
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 radiation
2003
Inactivating 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
2001
Escaping the stem cell compartment: Sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations
Zhang W, Remenyik E, Zelterman D, Brash D, Wikonkal N. Escaping the stem cell compartment: Sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 13948-13953. PMID: 11707578, PMCID: PMC61147, DOI: 10.1073/pnas.241353198.Peer-Reviewed Original Research
1996
Cellular proofreading
Brash D. Cellular proofreading. Nature Medicine 1996, 2: 525-526. PMID: 8616708, DOI: 10.1038/nm0596-525.Commentaries, Editorials and LettersRelationship Between Sunlight Exposure and a Key Genetic Alteration in Basal Cell Carcinoma
Gailani M, Leffell D, Ziegler A, Gross E, Brash D, Bale A. Relationship Between Sunlight Exposure and a Key Genetic Alteration in Basal Cell Carcinoma. Journal Of The National Cancer Institute 1996, 88: 349-354. PMID: 8609643, DOI: 10.1093/jnci/88.6.349.Peer-Reviewed Original ResearchConceptsBasal cell carcinomaLoss of heterozygosityCell carcinomaP53 geneSunlight exposureExact testGenetic alterationsPathogenesis of BCCSun-exposed areasFrequency of LOHMohs micrographic surgical techniqueEnvironmental agentsLocation of tumorFisher's exact testSkin cancer patientsKey genetic alterationsUVB radiationChi-squared analysisFrequent genetic alterationsLimited associationSpecific environmental agentsBCC incidenceTumor characteristicsCancer patientsCommon cancer
1993
Local recurrence versus new primary: Clinical analysis of 82 breast relapses and potential applications for genetic fingerprinting
Haffty B, Carter D, Flynn S, Fischer D, Brash D, Simons J, Ziegler A, Fischer J. Local recurrence versus new primary: Clinical analysis of 82 breast relapses and potential applications for genetic fingerprinting. International Journal Of Radiation Oncology • Biology • Physics 1993, 27: 575-583. PMID: 8226151, DOI: 10.1016/0360-3016(93)90382-6.Peer-Reviewed Original ResearchConceptsNew primary tumorsBreast relapsePrimary tumorTrue recurrenceNew primaryConservative surgeryLocal recurrencePathological criteriaRadiation therapyOriginal tumorSurvival rateClinical pathological analysisSecond primary tumorsShorter median timeTrue local recurrenceSignificant prognostic implicationsDNA flow cytometryLocal relapseMedian timePrognostic implicationsResidual diseaseTumor bedPathological analysisRelapseTherapeutic implications
1991
A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma.
Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, Halperin AJ, Pontén J. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 1991, 88: 10124-10128. PMID: 1946433, PMCID: PMC52880, DOI: 10.1073/pnas.88.22.10124.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaCell carcinomaP53 mutationsMajor epidemiologic risk factorsUV-induced p53 mutationsInvasive squamous cell carcinomaEpidemiologic risk factorsUV-specific mutationsP53 tumor suppressor geneInternal malignancySwedish patientsRisk factorsSkin cancerTumor progressionTT double-base changesTumor suppressor geneCarcinomaHuman cancersCancerDipyrimidine sitesSuppressor geneT substitutionSkinMutationsPatients
1990
Defective DNA Repair in Humans: Clinical and Molecular Studies of Xeroderma Pigmentosum
Kraemer K, Seetharam S, Seidman M, Bredberg A, Brash D, Waters H, Protić-Sablijć M, Peck G, DiGiovanna J, Moshell A, Tarone R, Jones G, Parshad R, Sanford K. Defective DNA Repair in Humans: Clinical and Molecular Studies of Xeroderma Pigmentosum. Basic Life Sciences 1990, 53: 95-104. PMID: 2282051, DOI: 10.1007/978-1-4613-0637-5_7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
1982
Determination of DNA superhelicity and extremely low levels of DNA strand breaks in low numbers of nonradiolabeled cells by DNA-4′,6-diamidino-2-phenylindole fluorescence in nucleoid gradients
Lipetz P, Brash D, Joseph L, Jewett H, Lisle D, Lantry L, Hart R, Stephens R. Determination of DNA superhelicity and extremely low levels of DNA strand breaks in low numbers of nonradiolabeled cells by DNA-4′,6-diamidino-2-phenylindole fluorescence in nucleoid gradients. Analytical Biochemistry 1982, 121: 339-348. PMID: 7103066, DOI: 10.1016/0003-2697(82)90491-2.Peer-Reviewed Original Research