MOLECULAR GENETIC FEATURES OF THYROID CANCER IN RESIDENTS OF THE KHOREZM REGION

Abstract Background. Thyroid cancer (TC) is the most common malignant tumor of the endocrine system and demonstrates pronounced molecular heterogeneity. Genetic alterations such as BRAF, RAS, RET/PTC, NTRK fusions, and TERT promoter mutations play a key role in tumor initiation, progression, and prognosis. Objective. To investigate the molecular genetic profile of thyroid cancer in residents of the Khorezm region and assess its association with clinicopathological characteristics. Materials and Methods. A combined retrospective–prospective study was conducted on surgically resected thyroid tumors from patients living in the Khorezm region. Histopathological diagnosis was established according to WHO Classification (2022). Molecular genetic analysis included detection of BRAF V600E, NRAS/HRAS/KRAS, TERT promoter mutations, and gene rearrangements (RET, NTRK) using PCR-based methods and next-generation sequencing (NGS). Results. Papillary thyroid carcinoma predominated among the studied cases. BRAF V600E mutation was the most frequent genetic alteration, followed by RAS mutations. TERT promoter mutations were detected mainly in tumors with aggressive morphological features. Gene rearrangements (RET/NTRK) were identified in a smaller proportion of cases. Conclusion. The molecular genetic landscape of thyroid cancer in the Khorezm region is characterized by a predominance of BRAF-dependent carcinogenesis with a subset of tumors demonstrating high-risk molecular markers. Integration of molecular diagnostics into routine practice improves risk stratification and supports personalized treatment strategies.