A Novel and Rapid System to Classify BRCA2 Missense and Other Variants in Ovarian Cancer
Abstract
Genetic screening is now recommended for all women diagnosed with ovarian cancer as a basis for guiding cancer prevention (such as oophorectomy) and treatment (such as PARP inhibitors). These procedures and treatments can potentially save lives. However, many of the genetic alterations found in screens of ovarian cancer genes like BRCA2 are variants of uncertain significance (VUS) which do not generally inform clinical care. As a basis for better interpreting the significance of missense BRCA2 VUS, we have developed an expression system to characterize their effects on homologous recombination and cellular resistance to PARP inhibitors. In the past year, we have generated expression constructs containing 8 benign and 8 pathogenic missense BRCA2 variants for validation of our system. We have also developed expression constructs and cells for 29 missense BRCA2 VUS for which we also have clinical/genetic data. Results of HR assays and clinical/genetic data for these VUS will be used for multifactorial statistical models of pathogenicity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2020
- Accession Number
- AD1115916
Entities
People
- Paul R. Andreassen
Organizations
- Ohio State University