title: A multi-institutional study of the prevalence of BRCA1 and BRCA2 large genomic rearrangements in familial breast cancer patients.
abstract: BACKGROUND
  Large genomic rearrangements (LGRs) in the BRCA1/2 genes are frequently observed in breast cancer patients who are negative for BRCA1/2 small mutations. Here, we examined 221 familial breast cancer patients from 37 hospitals to estimate the contribution of LGRs, in a nationwide context, to the development of breast cancer.
  
  
  METHODS
  Direct sequencing or mutation scanning followed by direct sequencing was performed to screen small mutations. BRCA1/2 small mutation-negative patients were screened for the presence of LGRs using a multiple ligation-dependent probe amplification (MLPA) assay.
  
  
  RESULTS
  Using a combined strategy to detect the presence of small mutations and LGRs, we identified BRCA1/2 small mutations in 78 (35.3%) out of 221 familial breast cancer patients and BRCA1 LGRs in 3 (2.1%) out of 143 BRCA1/2 small mutation-negative patients: the deletion of exons 11-13, the deletion of exons 13-15, and whole gene deletion of exons 1-24. The novel deletion of exons 11-13 is thought to result from a non-homologous recombination event mediated by a microhomology sequence comprised of 3 or 4 base pairs: c.3416_4357 + 1863delins187 (NG_005905.2: g.33369_44944delins187).
  
  
  CONCLUSIONS
  In this study, we showed that LGRs were found in 3.7% (3/81) of the patients who had mutations in BRCA1 or BRCA2, and 7.5% (3/40) of patients with mutations in BRCA1. This suggests that the contribution of LGRs to familial breast cancer in this population might be comparable to that in other ethnic populations. Given these findings, an MLPA to screen for mutations in the BRCA1 gene is recommended as an initial screening test in highly selective settings.
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.forename: Sung Im
authors.initials: SI
authors.lastname: Cho
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Kim
authors.forename: Il Yong
authors.initials: IY
authors.lastname: Chung
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Kang
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
authors.forename: Min Hyuk
authors.initials: MH
authors.lastname: Lee
authors.forename: Doo Ho
authors.initials: DH
authors.lastname: Choi
authors.forename: Cha Kyong
authors.initials: CK
authors.lastname: Yom
authors.forename: Woo-Chul
authors.initials: WC
authors.lastname: Noh
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Chang
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Sungnam, Korea. brcakorea@gmail.com.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human