Alma Rechav Ben Natan L&S Sciences
BRCA1 and BRCA2 High-Throughput Mutation Classification
Breast cancer is the most frequently diagnosed cancer in women – as high as 25%, while ovarian cancer accounts for 2.5% of cancers in women. Women who carry BRCA1 or BRCA2 non-functional mutations are predisposed to early onset of hereditary breast and ovarian cancer. There are many variants of uncertain significance (VUS) in the population, which are limiting the clinical utility of genetic information – they might not be sensitive to the current clinically used therapeutic drugs. PARP inhibition (PARPi) is currently the only therapeutic drug that is used for patients with BRCA1 or BRCA2 mutations. The lack of other therapeutic approaches currently prevents a comprehensive drug sensitivity annotation. It is important to understand which type of mutations are PARPi sensitive in order to optimize the choice of therapeutic strategy of patients carrying different BRCA1 or BRCA2 mutations. I aim to address the clinical challenge of BRCA1 and BRCA2 mutation classification, focusing mainly on identifying mutations that are sensitive to PARPi in order to generate an initial drug sensitivity map.