Improving performance of multigene panels for genomic analysis of cancer predisposition.

摘要: Screening multiple genes for inherited cancer predisposition expands opportunities prevention; however, reports of variants uncertain significance (VUS) may limit clinical usefulness. We used an expert-driven approach, exploiting all available information, to evaluate multigene panels in a series that included types and complex family histories. For 1,462 sequential patients referred testing by BROCA or ColoSeq panels, genomic DNA was sequenced were interpreted experts using International Agency Research on Cancer guidelines incorporating evolutionary conservation, known predicted variant consequences, personal history. Diagnostic yield evaluated various presenting conditions family-history profiles. Of patients, 12% carried damaging mutations established genes. varied presentation. Actionable results identified 13% breast colorectal 4% cancer-free subjects, based their histories cancer. Incidental findings explaining neither the patient nor present 1.7% subjects. Less than 1% VUS BRCA1 BRCA2. combined, initial contained 10.5% which declined 7.5% after reclassification additional information. Individualized interpretation gene is medical activity. Interpretation context maximizes actionable minimizes VUS. Genet Med 18 10, 974–981.