Analysis of BRCA1 large genomic rearrangements to identify individuals at risk of breast cancer

Abstract Background. Breast cancer (BC) is a malignant neoplasm in which genetic and environmental aspects contribute to its development. In many cases, pathogenic mutations in BRCA1 are caused by large genomic rearrangements such as copy number variations, a mechanism of gene inactivation that increases the risk of BC. Therefore, identifying women at high risk of BC through genetic testing is of great importance. This study aimed to identify large BRCA1 rearrangements in patients with early-onset or family history of BC. Methods. Peripheral blood from patients with (n= 38) and without (n= 30) BC was analyzed using the multiplex ligation-dependent probe amplification assay to detect large genomic rearrangements in BRCA1. Results. One patient with sporadic BC showed an ambiguous deletion in exon 12 of the BRCA1 gene. To validate this result, full sequencing of this region was performed. The mutation detected by MLPA resulted in a false positive, showing that large genomic rearrangements in BRCA1 were absent in all subjects. Moreover, in this same patient, we detected the presence of c.4308T>C (rs1060915) polymorphism. Conclusions. In our patients with BC, large genomic rearrangements in BRCA1 are held unaccountable for the development of the disease. We identified the presence of single nucleotide polymorphism, c.4308T>C (rs1060915), in a patient with sporadic BC.