title: Analysis of BRIP1 Variants among Korean Patients with BRCA1/2 Mutation-Negative High-Risk Breast Cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiation Oncology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
authors.forename: Haeyoung
authors.initials: H
authors.lastname: Kim
authors.affiliation: LabGenomics Clinical Research Institute, LabGenomics, Seongnam, Korea.
authors.forename: Dae-Yeon
authors.initials: DY
authors.lastname: Cho
authors.affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Doo Ho
authors.initials: DH
authors.lastname: Choi
authors.affiliation: LabGenomics Clinical Research Institute, LabGenomics, Seongnam, Korea.
authors.forename: Gee Hue
authors.initials: GH
authors.lastname: Jung
authors.affiliation: LabGenomics Clinical Research Institute, LabGenomics, Seongnam, Korea.
authors.forename: Inkyung
authors.initials: I
authors.lastname: Shin
authors.affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Park
authors.affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seung Jae
authors.initials: SJ
authors.lastname: Huh
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Gil
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D000072417:Protein Domains / Q000235:genetics; D020365:RNA Helicases / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D000069456:Silent Mutation; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D051856:Fanconi Anemia Complementation Group Proteins; C000618935:BRIP1 protein, human; D020365:RNA Helicases
keywords: BRCA1; BRCA2; BRIP1; Hereditary breast and ovarian cancer syndrome; Korea