Abstract. Breast cancer (BC) is one of the most common oncological diseases among women in the Russian Federation. With the development of sequencing technologies, it has become possible to search for causal mutations in various genes that contribute to carcinogenesis. The aim of this study was to characterize the spectrum of causal hereditary mutations in the BRCA1/BRCA2, CHEK2, PALB2, and ATM genes and the frequency of driver somatic mutations in the PIK3CA gene in a cohort of women with early-onset BC (under 40 years of age). The study included biological samples from 351 women with a mean age of 37.4 ± 4.9 years diagnosed with breast cancer (BC). Genomic DNA was isolated from whole blood samples from all patients and from 15 synchronous tumor tissue samples. The obtained DNA preparations were used to prepare genetic libraries using the Solo-test ABC Plus multigene panel (OncoAtlas, Russia). High-throughput sequencing (NGS) of the prepared libraries was performed on the MiSeq (Illumina, USA) and FASTASeq 300 (GeneMind, China) platforms. The study was constructed using a retrospective design. In the study group, 50 pathogenic variants were identified in the BRCA1/BRCA2 genes (14.2 %), 12 in CHEK2 (3.4 %), 6 in ATM (1.7 %), and 2 in PALB2 (0.6 %). In addition to pathogenic variants, variants in the CHEK2 gene that increase the risk of developing breast cancer were detected in 6 patients. In a sample of 351 patients, pathogenic variants of 3 genes (CHEK2, PALB2, ATM) were detected in 5.7 % of cases, which, together with mutations in the BRCA1 and BRCA2 genes, explains 20 % of breast cancer cases. Mass analysis of the CHEK2, PALB2, and ATM genes allows for significant improvements in the diagnostics of hereditary forms of breast cancer.
Key words: breast cancer; NGS; CHEK2; PALB2; ATM; BRCA1; BRCA2
For citation: Orlov P.S., Bredikhin D.A., Lebedeva A.A., Taraskina A.A., Grigorieva T.V., Subbotovskaya A.I., Voevoda M.I. Spectrum of pathogenic variants in the CHEK2, PALB2, and ATM genes in Russian patients with breast cancer. Pisma v Vavilovskii Zhurnal Genetiki i Selektsii = Lett Vavilov J Genet Breed. 2026. Online first. doi 10.18699/letvjgb-2026-12-14
Funding. The study was partially carried out within the budget project FWNR -2026-0027 of the ICG SB RAS, it was carried out in the Centre for Collective Usage “Proteomic Analysis”.