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

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 cancer...

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Detalles Bibliográficos
Autores principales: Kim, Haeyoung, Cho, Dae-Yeon, Choi, Doo Ho, Jung, Gee Hue, Shin, Inkyung, Park, Won, Huh, Seung Jae, Nam, Seok Jin, Lee, Jeong Eon, Gil, Won Ho, Kim, Seok Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Cancer Association 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946366/
https://www.ncbi.nlm.nih.gov/pubmed/26790966
http://dx.doi.org/10.4143/crt.2015.191
Descripción
Sumario: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.