The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus
Jimenez-Sainz J, Krysztofiak A, Garbarino J, Rogers F, Jensen RB. The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus. Frontiers In Genetics 2022, 13: 884210. PMID: 35711920, PMCID: PMC9197106, DOI: 10.3389/fgene.2022.884210.Peer-Reviewed Original ResearchDominant-negative alleleDNA damage responseDNA repair functionDNA strand exchangeHomology-directed repairGenome instabilityCellular functionsDamage responseDNA bindingNegative allelesStrand exchangeRepair functionGermline missense variantsCell survivalFunction mutationsMissense variantsRAD51Pathogenic allelesSimple lossPARP inhibitorsCytoplasmProteinAllelesHomologyDNAImprecise 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 variantsPatients