Search for pathogenic changes in BRCA1/2 genes using mass parallel sequencing technology in patients with breast and ovarian cancer from the Republic of Bashkortostan

Abstract

A study was carried out to identify the spectrum and frequency of pathogenic changes in the BRCA1 and BRCA2 genes in tumor tissue preparations of 70 women with triple negative breast cancer (TNBC) and 50 women with serous type of ovarian malignant neoplasms (ON) from the Republic of Bashkortostan using a new generation sequencing technology (NGS). Thus, 27 pathogenic variants were identified in the BRCA1/2 genes were identified (14 in the BRCA1 gene and 9 in the BRCA2 gene) in 38.0% of women with ON and 41.4% of patients with TNBC. Mutations c.181T> G (rs886040898) and c.5266dupC (rs80357906) in the BRCA1 gene were found in women with both TNBC and ON, other pathogenic changes did not intersect. In the BRCA1 gene, 7 pathogenic and 1 probably pathogenic variant were identified in women with breast cancer, the most common mutation was c.5266dupC, which was found in 17.14% of women. The second most frequent mutation c.181T> G- was found in 4.29% of women with TNBC, the third c.3700_3704del - 2.86%. Mutations c.1918C> T, c.3779T> G, c.5453A> G, c.68_69delAG were found in isolated cases. The c.5266dupC mutation in the BRCA1 gene was also the most frequent in patients with ON (10%). The c.4035delA mutation was found in two patients, the remaining 7 mutations were found in isolated cases. In the BRCA2 gene, 5 pathogenic and 2 probable pathogenic variants were identified in patients with TNBC, as well as 4 pathogenic and 2 probable pathogenic variants in women with ON, each mutation was detected in only one woman and is a unique variant not found in other patients. The results obtained demonstrate the high efficiency of mass parallel sequencing for searching for mutations in targeted genes in tumor tissue.