Genetic diagnosis of hereditary and sporadic forms of medullary thyroid cancer: clinical importance and perspectives

Medullary thyroid cancer is a rare neuroendocrine tumor that originates from parafollicular C-cells. The etiology of the disease can be either sporadic or hereditary, and it is associated with multiple endocrine neoplasia syndromes types 2A and 2B. Genetic analysis of sporadic MTC reveals significant variation when compared to hereditary forms of the disease. This review paper summarizes current data on the frequency and prognostic significance of RET and RAS mutations, providing information on the molecular genetic characterization of MTC and the possibilities of personalized therapy with tyrosine kinase inhibitors. An examination of the approaches to molecular diagnostics is undertaken, with particular emphasis on their clinical significance in verifying diagnoses, assessing the risk of relapse, and selecting therapy. A thorough analysis of recent data on the frequency of somatic mutations in sporadic forms of breast cancer, their mutual exclusivity, and their relationship to the biological behavior of the tumor is presented herein.