Imprecise Medicine: BRCA2 Variants of Uncertain Significance (VUS), the Challenges and Benefits to Integrate a Functional Assay Workflow with Clinical Decision Rules
Jimenez-Sainz J, Jensen RB. Imprecise Medicine: BRCA2 Variants of Uncertain Significance (VUS), the Challenges and Benefits to Integrate a Functional Assay Workflow with Clinical Decision Rules. Genes 2021, 12: 780. PMID: 34065235, PMCID: PMC8161351, DOI: 10.3390/genes12050780.Peer-Reviewed Original ResearchConceptsCancer riskFunctional assaysUncertain significanceSomatic BRCA2 mutationClinical decision ruleFuture cancer riskClinical decision processBRCA2 VUSBiochemical functional assaysClinical findingsTherapeutic optionsTreatment optionsPancreatic cancerBRCA2 mutationsClinical guidancePlatinum agentsPathological outcomesBenign naturePARP inhibitorsBRCA2 genesGermline mutationsPathological impactAccurate functional assaysBRCA2 variantsPatientsThe Tumor-Associated Variant RAD51 G151D Induces a Hyper-Recombination Phenotype
Marsden CG, Jensen RB, Zagelbaum J, Rothenberg E, Morrical SW, Wallace SS, Sweasy JB. The Tumor-Associated Variant RAD51 G151D Induces a Hyper-Recombination Phenotype. PLOS Genetics 2016, 12: e1006208. PMID: 27513445, PMCID: PMC4981402, DOI: 10.1371/journal.pgen.1006208.Peer-Reviewed Original ResearchMeSH KeywordsBRCA2 ProteinBreast NeoplasmsChromosome AberrationsDNA Breaks, Double-StrandedDNA DamageDNA RepairDoxorubicinFemaleGene Expression Regulation, NeoplasticGenomic InstabilityHumansMCF-7 CellsMitomycinMutationRad51 RecombinaseRadiation, IonizingRecombinational DNA RepairSister Chromatid ExchangeConceptsHuman breast epithelial cellsBreast epithelial cellsSister chromatid exchangesBreast carcinomaDrug resistanceMitomycin CEpithelial cellsChromosomal aberrationsHigh levelsChromatid exchangesRepairSomatic variantsRAD51 variantsDNA damageMultiple DNA damaging agentsDNA damaging agentsPresence of RPAPhenotypeCellsCarcinomaExpressionDNA double-strand breaksDamaging agentsLevelsVariantsPromotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry
Zhao W, Vaithiyalingam S, San Filippo J, Maranon DG, Jimenez-Sainz J, Fontenay GV, Kwon Y, Leung SG, Lu L, Jensen RB, Chazin WJ, Wiese C, Sung P. Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry. Molecular Cell 2015, 59: 176-187. PMID: 26145171, PMCID: PMC4506714, DOI: 10.1016/j.molcel.2015.05.032.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionBRCA2 ProteinBreast NeoplasmsCell LineFemaleHeLa CellsHomologous RecombinationHumansModels, BiologicalMolecular MimicryMutagenesis, Site-DirectedNuclear Magnetic Resonance, BiomolecularProteasome Endopeptidase ComplexProtein SubunitsRad51 RecombinaseRecombinant ProteinsReplication Protein AConceptsReplication protein AHomologous recombinationAffinity of RPAReplication fork repairTumor suppressor BRCA2DNA mimicryGenome maintenanceFork repairMediator complexRAD51 recombinaseAcidic domainDNA breaksBiological processesTumor suppressionDSS1Vivo analysisProtein ADNA mimicsSsDNARecombinationBRCA2ComplexesRecombinaseDNAMutations