Searching for large genomic rearrangements of the BRCA1 gene in a Nigerian population

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...

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Bibliographic Details
Published in:Breast cancer research and treatment 2010-11, Vol.124 (2), p.573-577
Main Authors: Zhang, Jing, Fackenthal, James D, Huo, Dezheng, Zheng, Yonglan, Olopade, Olufunmilayo I
Format: Article
Language:English
Subjects:
Adult
African Continental Ancestry Group - genetics
Alu-element
Analysis
Base Sequence
Biological and medical sciences
BRCA1
BRCA1 Protein - genetics
Breast cancer
breast neoplasms
Breast Neoplasms - ethnology
Breast Neoplasms - genetics
Breast Neoplasms, Male - ethnology
Breast Neoplasms, Male - genetics
Brief Report
Cancer
Cancer research
Chromosome Breakpoints
Exons
Female
Gene mutations
Gene Rearrangement
Genes
Genetic aspects
Genetic Predisposition to Disease
Genomics
Gynecology. Andrology. Obstetrics
Humans
Introns
Large genomic rearrangements
Male
Mammary gland diseases
Medical sciences
Medicine
Medicine & Public Health
Middle Aged
Molecular Sequence Data
Nigeria - epidemiology
Nigerian
Oncology
Ovarian cancer
Polymerase Chain Reaction
Risk Assessment
Risk Factors
Sequence Deletion
Toy industry
Tumors
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Summary: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.
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-010-1006-9