Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test

PURPOSE: Hereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an next-generation sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC). MATERIALS AND METHODS: A total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017. RESULTS: Of 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1. CONCLUSION: NGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.