Analysis of BRIP1 Variants among Korean Patients with BRCA1/2 Mutation-Negative High-Risk Breast Cancer.
- Author:
Haeyoung KIM
1
;
Dae Yeon CHO
;
Doo Ho CHOI
;
Gee Hue JUNG
;
Inkyung SHIN
;
Won PARK
;
Seung Jae HUH
;
Seok Jin NAM
;
Jeong Eon LEE
;
Won Ho GIL
;
Seok Won KIM
Author Information
- Publication Type:Original Article
- Keywords: BRIP1; BRCA1; BRCA2; Hereditary breast and ovarian cancer syndrome; Korea
- MeSH: Breast Neoplasms*; Breast*; Computer Simulation; Electrophoresis; Exons; Genetic Variation; Hereditary Breast and Ovarian Cancer Syndrome; Humans; Introns; Korea; Silent Mutation
- From:Cancer Research and Treatment 2016;48(3):955-961
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: The aim of the current study is to assess the spectrum of genetic variation in the BRIP1 gene among Korean high-risk breast cancer patients who tested negative for the BRCA1/2 mutation. MATERIALS AND METHODS: Overall, 235 Korean patientswith BRCA1/2 mutation-negative high-risk breast cancerwere screened for BRIP1 mutations. The entire BRIP1 gene was analyzed using fluorescent-conformation sensitive gel electrophoresis. In silico analysis of BRIP1 variants was performed using PolyPhen-2 and SIFT. RESULTS: A total of 20 sequence alterations including 12 exonic and eight intronic variantswere found. Among the 12 exonic variants, 10 were missense and two were silent mutations. No protein-truncating mutation was found among the tested patients. Among the 10 missense variants, four (p.L263F, p.L340F, p.L474P, and p.R848H) were predicted to be pathogenic by both PolyPhen-2 and SIFT, and these variants were found in five patients. Of the four missense variants, p.L263F, p.L474P, and p.R848H localize to regions between the helicase motifs, while p.L340F resides in an iron-sulfur domain of BRIP1. CONCLUSION: No protein-truncating mutation in BRIP1 was found among the tested patients. The contribution of BRIP1 variants is thought to be minor in Korean non-BRCA1/2 high-risk breast cancer.
