NEW YORK (GenomeWeb) – By systematically introducing mutations into the BRCA1 gene, researchers have sought to better classify which variants are likely to be pathogenic or benign.
BRCA1 is one of the best-studied genes, but the impact of its numerous variants on breast and ovarian cancer risk remains unclear. Such variants of uncertain significance (VUS) limit the clinical utility of a patient’s data, said the authors of the new study.
“Frequently women are being tested for BRCA1 mutations because they have a family history of breast or ovarian cancer,” paper co-author Lea Starita from the University of Washington said in a statement. “To be told that they have a genetic variant in this cancer-predisposing gene, but that the doctor doesn’t know what it means, does not reduce their stress or their anxiety.”
Using saturation genome editing, she and her colleagues tested how changes to 13 exons in the BRCA1 gene affected cells’ abilities to grow in culture and see whether those alterations affect gene function. As they reported in Nature today, the variants determined by the researchers to be functional highly corresponded with what has been reported in the ClinVar database.
The researchers focused their saturation editing on the 13