Cancer Res Treat.  2016 Jul;48(3):955-961. 10.4143/crt.2015.191.

Analysis of BRIP1 Variants among Korean Patients with BRCA1/2 Mutation-Negative High-Risk Breast Cancer

• Kim H
• Cho DY
• Choi DH
• Jung GH
• Shin I
• Park W
• Huh SJ
• Nam SJ
• Lee JE
• Gil WH
• Kim SW

• KMID: 2344068
• DOI: http://doi.org/10.4143/crt.2015.191

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.

Keyword

BRIP1; BRCA1; BRCA2; Hereditary breast and ovarian cancer syndrome; Korea

MeSH Terms

Breast Neoplasms*
Breast*
Computer Simulation
Electrophoresis
Exons
Genetic Variation
Hereditary Breast and Ovarian Cancer Syndrome
Humans
Introns
Korea
Silent Mutation

Reference

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