Abstract P1-08-08: Heterozygous germline mutations in RAD50 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation

Background: The MRE11-RAD50-nibrin (MRN) complex participates in pathways of double-strand break induced DNA repair and cell cycle checkpoint control. RAD50 interacts with the MRE11 and NBS proteins, is involved in the maintenance of genomic integrity. The association of RAD50 mutation and breast cancer susceptibility has been reported in European patients. However, the impact of RAD50 mutation on a breast cancer predisposition among Koreans remains uncertain. In the current analysis, we evaluated the incidence of RAD50 mutations among Korean patients with non-BRCA1/2 high-risk breast cancer. Materials and Methods: A total of 247 Korean patients with high-risk breast cancer who tested negative for BRCA1/2 mutation were enrolled. The criteria for high-risk breast cancer were as follows: having a family history of breast or ovarian cancer in any relative; diagnosed at age 40 years or younger; bilateral breast cancer; and male breast cancer. All participants were screened for BRCA1/2 mutations using fluorescent-conformation sensitive capillary electrophoresis (F-CSCE) and traditional sequencing. The entire RAD50 gene of each patient was sequenced using F-CSCE. In silico analyses of the RAD50 variants was performed using PolyPhen-2 and SIFT. Results: There were two novel deleterious mutations in RAD50 (p.Q426X, p.E1271del). These mutations were found in two patients, including one with p.Q426X and the other with p.E1271del. Besides, five sequence variants in RAD50 were identified: four exonic variants (p.I118T, p.R486C, p.L1264F, and p.R1279H) and one intronic variant (c.1246-11T>C). Among the four missense variants, p.R486C and p.L1264F were variants predicted to be deleterious by in silico analyses. Conclusions: We found protein-truncating mutations in RAD50 gene in a small proportion of Korean patients with high-risk breast cancer. The contribution of the mutation to the development of breast cancer should be clarified in further researches. Citation Format: Kim H, Cho D-Y, Choi DH, Jung GH, Shin I, Park W, Huh SJ, Nam SJ, Lee JE, Gil WH, Kim SW. Heterozygous germline mutations in RAD50 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-08-08.