👤 Polina Gervas

The BRCA1/2 mutation status testing is the global standard of care for breast cancer patients with a family history of cancer. BRCA1/2 mutations are known to be ethno-specific. For some ethnic groups of the Northern Asia (Buryats, Yakuts, Altaians, Tuvans, Khakasses, etc.) the founder mutations in the BRCA1/2 genes have not been revealed. This systematic review was conducted to assess the prevalence of BRCA1/2 mutation in breast cancer patients inhabiting Eastern Europe and Northern Asia (or Siberia). A total of 23,561 studies published between 2014 and 2024 were analyzed, of which 55 were included in the review. The literature search was conducted using RusMed, Cyberleninka, Google Scholar, eLibrary, NCBI databases (n=5) and conference papers. The founder mutations (c.5266dupC and/or c.181T>G) of BRCA1 gene that were frequently observed in the Slav peoples were also identified in Chechens, Armenians, Bashkirs, Ukrainians, Mordovians, Mari, Kabardians, Tatars, Uzbeks, Kyrgyz, Ossetians, Khanty indigenous peoples and Adygs. For Chechens, Kabardians, Ingush, Buryats, Khakasses, Sakha, Tuvans and Armenians, rare pathogenic variants of the BRCA1/2, ATM, СНЕК2, BRIP1, NBN, PTEN, TP53, PMS1, XPA, LGR4, BRWD1 and PALB2 genes were found. No data are available about the frequency of pathogenic BRCA1/2 mutations for ethnic groups, such as the Udmurts, Komi, Tajiks, Tabasarans, and Nogais indigenous people. This is the first systematic review that provides the spectrum of BRCA mutations in ethnic groups of breast cancer patients inhabiting Eastern Europe and Northern Asia. It has been shown that the mutations are ethnospecific (varied widely within groups) and not all groups are equally well studied. Further studies on the ethnic specificity of BRCA gene mutations are required. Show less

Whole exome sequencing of peripheral blood samples from Tuvan females diagnosed with breast and ovarian cancers (BC/OC) was performed to search for new genes involved in BC/OC pathogenesis. Considering the high cost of whole exome sequencing and study material requirements, 9 samples were selected from 61 genomic DNA samples. A mutation in the LGR4 gene (rs34804482) involved in the tumor-mediated Wnt signaling pathway and a mutation in the BRWD1 gene (rs147211854) involved in chromatin remodeling were identified in BC patients. A mutation in the CITED2 gene (rs77963348) involved in the pathogenesis of primary ovarian insufficiency was identified in a patient with OC and a history of infertility. A mutation in the PDGFRA gene (rs2291591) was identified in two BC/OC patients. LRG4, BRWD1, PDGFRA, and CITED2 germline pathogenic mutations were discovered in Tuvan women diagnosed with BC/OC for the first time. Show less