BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair
Jimenez-Sainz J, Mathew J, Moore G, Lahiri S, Garbarino J, Eder JP, Rothenberg E, Jensen RB. BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair. ELife 2022, 11: e79183. PMID: 36098506, PMCID: PMC9545528, DOI: 10.7554/elife.79183.Peer-Reviewed Original ResearchConceptsHomology-directed repairDNA double-strand breaksFork protectionReplication fork protectionRad51 nucleoprotein filamentsMissense mutationsSingle amino acid substitutionRad51-ssDNA complexesDouble-strand breaksUnknown functional consequencesBRCA2 VUSAmino acid substitutionsGenome stabilityNucleoprotein filamentDNA repairRepeat regionSpacer regionBRCA2 proteinBenign allelesCellular responsesAcid substitutionsFunctional consequencesFrameshift mutationGene predisposeBRC2Imprecise 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