2 Landscape of Germline Mutations in DNA Repair Genes for Breast Cancer in a Multinational Region Located in the Southeast of the European Part of Russia

Miami Breast Cancer Conference® Abstracts Supplement, 38th Annual Miami Breast Cancer Conference® - Abstracts, Volume 35, Issue suppl 1
Pages: 41-42

Pushkarev Vasili Alexandrovich, DMSc1; Musin Shamil Ismagilovich1; Sultanbaev Alexander Valerievich1; Nasretdinov Ainur Fanutovich1; Menshikov Konstantin Viktorovich1; Pushkarev Aleksey Vasilievich1

1State Autonomous Institution of Healthcare Republican Clinical Oncology Dispensary of Ministry of Healthcare of Republic Bashkortostan, Ufa, Russia.


Hereditary breast cancer is among the most common genetic pathologies, accounting for 15% to 20% of all breast cancer cases; it is mainly due to mutations in BRCA1/2 genes. In a small number of patients, this disease is connected with mutations in genes CHEK2, TP53, MSH2, ATM, PTEN, NBS1, BRIP1, PALB2, BARD1, STK11, MLH1, BLM, CDH1, and RAD50, accounting for 5% to 10% of all cases.

Materials and Methods

We analyzed blood from 100 unrelated patients who had a histologically confirmed diagnosis of breast cancer. The study was carried out using next-generation sequencing (NGS).


By using an NGS method, highly penetrant mutations in BRCA1, BRCA2, CHEK2, PALB2, and RAD50 were revealed in 16 patients. This method detected mutations in a total of 28 patients. Of a total of xx probands in the BRCA1 gene, mutations were detected in 13 patients: 12 patients with the 5382insC mutation and 1 patient with c.3143delG. In the BRCA2 gene, mutations were revealed in 3 patients: 2 patients with c.6621_6622del and 1 patient with c.-39-1_-39delGA. Mutations in CHEK2 were detected in 5 patients: c.470T>C in 3 patients and c.444+1G>A in 2 patients. The 1592delT mutation in PALB2 was found in 4 patients. The c.2157delA mutation in RAD50 was detected in 3 patients. A pedigree was compiled for each patient to define relatives who are likely carriers of mutations. A total of 237 blood relatives of probands, who are potential carriers of pathogenic mutations, were identified. At the initial stage of the study, 24 of 50 relatives of patients had pathogenic mutations: 4153delA and 5382insC in the BRCA1 gene, and mutation 6174delT in the BRCA2 gene. When pathogenic mutations were identified, measures were taken to prevent and/or provide early diagnosis of malignant neoplasms.


Pathogenic mutations in BRCA1/2, CHEK2, PALB2 and RAD50 were found in 28 patients with a hereditary feature of the disease. The identification of highly penetrant mutations in probands allowed us to determine their relatives, probable carriers of mutations, who were referred for genetic counseling. Early detection of pathogenic mutations, combined with identifying blood relatives of cancer patients, can help prevent the development of malignant neoplasms in a healthy population.