title: Exome sequencing in a breast cancer family without BRCA mutation.
abstract: OBJECTIVE
  We performed exome sequencing in a breast cancer family without BRCA mutations.
  
  
  METHODS
  A family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members.
  
  
  RESULTS
  We identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined.
  
  
  CONCLUSIONS
  Using exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies.
authors.affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jae Myoung
authors.initials: JM
authors.lastname: Noh
authors.affiliation: LabGenomics Clinical Research Institute, LabGenomics, Seongnam, Korea.
authors.forename: Jihun
authors.initials: J
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: 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
keywords: BRCA; Breast neoplasms; Exome