Study of the mutational landscape of primary foci and metastases of papillary carcinoma in the BRAF, KRAS and EGFR genes, their relationship with the clinical characteristics of the tumor

Introduction. Due to the rapidly growing incidence of tumor pathology of the thyroid gland, the range of molecular genetic research methods used to study the targets of targeted drugs, prognosis and surgical tactics is growing. Aim. To study the frequency of mutations of the BRAF, KRAS, EGFR genes in neoplastic diseases of the thyroid gland, their relationship with Bethesda categories at the preoperative stage, invasion and the presence of metastases. Methods. The material was taken from FFPE blocks of the thyroid glands of operated patients. DNA analysis was carried out on 73 histologically verified samples: 53 with papillary carcinoma (11 of them – follicular variant, 42 – classic), 16 – with follicular adenoma, 4 – with autoimmune thyroiditis. We used DNA extraction and real-time PCR with Test-Gen reagents, Russia. Comparisons were made using the Pearson chi-square test. Results. In the classic variant of papillary carcinoma, the BRAF V600E mutation is more often detected; in the follicular variant of papillary carcinoma, the following mutations are identified: BRAF, and more often BRAF V600K, as well as EGFR, KRAS. In follicular adenoma, mutations were found only in the KRAS gene. In most cases, the BRAF V600E mutation was found in patients with the classic variant of papillary carcinoma, having a Bethesda VI category at the preoperative stage. The BRAF V600K mutation is also more common among patients with Bethesda category VI, and the absence of this mutation is associated with female gender and lack of tumor vascular invasion. When analyzing the status of genes in primary tumors and metastases, discordance in the BRAF gene was revealed, which indicates the possible development of such clonal evolution of the tumor. Conclusion. The ability to identify key genes involved in the development of oncotransformation of the thyroid epithelium is promising and contributes to personalization and selection of drugs that affect oncogenesis.