Molecular genetics and clinical implications of medullary thyroid carcinoma and mutations of the RET protooncogene

Abstract

Distinct types of thyroid neoplasms are associated with mutations in specific genes. Medullary thyroid carcinoma (MTC) constitutes about 5% of all thyroid, neoplasms and can occur either as a sporadic tumor or in the context of the familial cancer syndromes multiple endocrine neoplasia types 2A and 2B and familial MTC. At least 23 different missense mutations in nine distinct codons of the RET protooncogene have been identified in hereditary MTC (in about 90% of all families investigated) and in sporadic MTC (in about 55% of the cases investigated). Presymptomatic DNA diagnosis of hereditary MTC; discrimination between hereditary and sporadic MTC; genotype-phenotype correlations; and future prospects with respect to therapy are reviewed in this paper, as well as the molecular pathophysiology of MTC and implications for the clinical management of hereditary and sporadic MTC.