title: Searching for large genomic rearrangements of the BRCA1 gene in a Nigerian population.
abstract: BRCA1/2 germline mutations predispose to breast and ovarian cancer. Large genomic rearrangements (LGRs) have widened the mutational spectrum of the BRCA1 gene, but the frequencies vary in different populations. In this study, we want to determine the spectrum of LGRs in BRCA1 gene in Nigerian breast cancer patients. The multiplex ligation-dependent probe amplification (MLPA) assay was used to screen BRCA1 rearrangements in 352 patients who previously tested negative for BRCA1 and BRCA2 point mutations and small insertions/deletions. Positive MLPA result was confirmed and located by long-range PCR. The breakpoints of the candidate rearrangement were characterized by sequencing. A novel deletion of BRCA1 exon 21 (c.5277 + 480_5332 + 672del) was detected in 1 out of 352 Nigerian breast cancer patients (0.3% occurrence frequency). Further analysis of breakpoints revealed that the deletion involves two Alu-elements: one AluSg in intron 20 and the AluY in intron 21. These data suggest that while BRCA1 genomic rearrangement exists, they do not contribute significantly to BRCA1-associated risk in the Nigerian population.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 900 E. 57th Street, KCBD Room 8240, Chicago, IL 60637, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: James D
authors.initials: JD
authors.lastname: Fackenthal
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
authors.forename: Yonglan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000208:ethnology / Q000235:genetics*; D056905:Chromosome Breakpoints; D005091:Exons; D005260:Female; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009549:Nigeria / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D017384:Sequence Deletion
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human