The spectrum of BRCA1 gene mutations in early onset breast cancer patients from Russia

Abstract

Aim of the study. Aim of the study was to estimate the occurrence of pathogenic mutations in the BRCA1 gene in Russian breast cancer patients.Material and methods. Complete coding sequence of the BRCA1 gene of 445 early onset breast cancer patients (under 40 years) from Novosibirsk region (Russia) were analyzed by targeted Next Generation Sequencing (NGS) using Ion Torrent platform. Results. Forty (9%) carriers of various pathogenic mutations were revealed. Thirty five (7,9%) patients carried 5382insC mutation, described earlier as a founder mutation for Slavic population. Five (1.1%) patients carried various pathogenic mutations, namely C61G, 462delCC, E143X, 4153delA, and IVS18+1G>T. Besides, 29 genetic variants with no clinical significance or with unknown clinical significance were detected in BRCA1 gene among 445 early onset breast cancer patients. Conclusions. Data on the frequency of genetic variations in the BRCA1 gene among early onset breast cancer patients in the Novosibirsk Region (Russia) were obtained. Proportion of the 5382insC mutation is 87.5% of all pathogenic mutations in the BRCA1 gene found in patients.

Application Areas of Traditional Molecular Genetic Methods and NGS in relation to Hereditary Urological Cancer Diagnosis

“…Comparing the cost of two-stage testing in these populations against a general NGS-based approach, the cost of targeted NGS panels for the diagnosis of hereditary PC per analysis for one patient ranges from $250 to $1,500, depending on how many loci are included in the panel in addition to BRCA1/2 [69]. Because the proportion of the 5382insC mutation among patients in East Slavic populations can exceed 50%, a simple and cheap (<$100) test based on real-time PCR would allow determination of the major BRCA1 mutation in half of the tested patients within 1 day [79,80] (unfortunately, a significant proportion of publications on this subject do not have an English version). However, we emphasize that such a twostage search for a pathogenic mutation in the BRCA1/2 genes can be performed only with sufficient clinical, genealogical, and population justification.…”