Mechanism of and research progress on alterations in the RET gene in thyroid cancer (Review)

The global incidence of thyroid cancer (TC) has markedly increased in recent years, making it the most prevalent endocrine‑related cancer worldwide. TC primarily originates from follicular and parafollicular cells of the thyroid gland, and includes four main pathological types: Papillary TC (PTC), follicular TC, medullary TC (MTC) and anaplastic TC. Notably, characteristic oncogenes and tumor suppressor genes are associated with TC, which are considered targets for the development of treatment strategies. The rearranged during transfection (RET) gene serves a pivotal role in the development of TC, and mutations and fusions of this gene are closely associated with the onset of MTC and PTC. The structure of RET includes four cadherin‑like domains and 16 cysteine residues in its extracellular domain, which confer unique functionalities and contribute to its intracellular role. RET activation is a complex process involving multiple intracellular events, including calcium ion binding, glial cell line‑derived neurotrophic factor family ligand binding, and RET receptor aggregation, dimerization and autophosphorylation. The present study reviews the structure and function of the RET proto‑oncogene and its pathogenic roles in various TC subtypes.