What are the molecular consequences of germline mutations in breast and ovarian cancer susceptibility genes in a Norwegian breast and ovarian cancer population?

Abstract

It is estimated that 5-10% of breast cancers (BC) and 25% of ovarian cancers (OC) are caused by inherited sequence variants in genes. In the mid 90’s, the two genes BRCA1 and BRCA2 were discovered to be directly associated with increased risk of BC and OC. Molecular screening of these two genes has revealed several disease causing variants as well as variants of unknown clinical significance (VUS). In this study, we investigated several BRCA1/2 VUSs for their impact on gene expression and protein product. Additionally, we investigated patients with BC and/or OC for disease causing variants in 92 additional genes. We identified five BRCA1/2 variants affecting the gene expression and/or protein product and further identified 13 patients with disease causing variants in other genes, demonstrating the need for broader genetic evaluation of patients with BC and OC.