It is known that breast cancer is a complex heterogeneous disease due to the presence or absence of overexpression of receptors on the surface of tumor cells that correlate with the presence of penetrant mutations. Malignant neoplasms are considered as genetic diseases if they are characterized by multiple mutations in the genome, or epigenetic changes at the DNA level. Hereditary forms of malignant neoplasms occupy a special position due to their frequent development at a young age.
The study was carried out using next-generation sequencing-NGS. A genetic blood test was performed on 30 patients with breast cancer.
As a result, highly penetrant mutations in the BRCA1, BRCA2, CHEK2, PALB2, RAD50 genes were revealed in 30 patients. Of the total share of probands in the BRCA1 gene mutations were detected with a mutation of 5382insC - 12 patients, c.3143delG- 3. In the BRCA2 gene of patients mutation c.6621_6622del- in 2 people and s. -39-1_-39delGA- in 1 patient. Using IHC a basal-like subtype breast cancer was established in all patients. The mutations were detected in the CHEK2 gene in 5 patients: c.470T> C- in 3 patients with a luminal B (HER2 positive) subtype; c.444 + 1G> A- in 2 patients with HER2 positive (non-luminal). In the PALB2 gene of cases: all 4 people with a basal-like subtype with the 1592delT mutation. The mutations c. 2157delA were detected in the RAD50 gene in 3 patients: of which 2 had luminal B (HER2 negative), 1 had luminal A subtype of breast cancer.
A next-generation sequencing method has significantly improved the efficiency of detecting mutations in the genes responsible for hereditary breast cancer. Pathogenic mutations in the BRCA1 / 2, CHEK2, PALB2, RAD50 genes were found of patients with a hereditary feature of the disease (proband has 1 to 3 blood relatives with malignant neoplasms). The identification of highly penetrant mutations in probands allowed us to determine their relatives, the expectable carriers of mutations, which were informed of the need genetic counseling.
Sultanbaev Alexander.
Has not received any funding.
All authors have declared no conflicts of interest.