Cancer Res Treat.  2020 Jul;52(3):697-713. 10.4143/crt.2019.559.

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

Affiliations
  • 1Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
  • 2Department of Surgery, Seoul National University Hospital, Seoul, Korea
  • 3Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, Seoul, Korea
  • 4Center for Medical Innovation, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea
  • 5National Cancer Center-Graduate School for Cancer Science and Policy, Goyang, Korea
  • 6College of Veterinary Medicine, Konkuk University, Seoul, Korea
  • 7Clinical Genomics Analysis Branch, Research Institute, National Cancer Center, Goyang, Korea
  • 8Center for Breast Cancer, Hospital, National Cancer Center, Goyang, Korea
  • 9Translational Cancer Research Branch, Division of Translational Science, National Cancer Center, Goyang, Korea
  • 10Cancer Research Institute, Seoul National University, Seoul, Korea
  • 11Genetic Counseling Clinic, Hospital, Department of System Cancer Science, Graduate School of Cancer Science and Policy, Goyang, Korea

Abstract

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 nextgeneration 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.

Keyword

Germline mutation; Next-generation sequencing; Breast cancer; Hereditary breast and ovarian cancer syndrome
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