Open AccessA Primer on the Genetics of Medullary Thyroid Cancer
Author(s) -
Vincent Larouche,
Amit Akirov,
Carissa M. Thomas,
Monika K. Krzyzanowska,
Shereen Ezzat
Publication year - 2019
Publication title -
current oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.053
H-Index - 51
eISSN - 1718-7729
pISSN - 1198-0052
DOI - 10.3747/co.26.5553
Subject(s) - multiple endocrine neoplasia type 2 , medullary thyroid cancer , medicine , germline mutation , germline , multiple endocrine neoplasia , thyroid , thyroid cancer , pheochromocytoma , pathology , cancer , medullary cavity , ret proto oncogene , cancer research , mutation , genetics , biology , gene
Medullary thyroid cancer is a rare type of neuroendocrine tumour that arises from the parafollicular cells (C cells) of the thyroid gland. It accounts for 3%–5% of thyroid cancer cases. Close to 25% of cases are familial, and 75% are considered sporadic. Familial cases are associated with a germline RET mutation; 43%–65% of sporadic cases harbour a somatic event in the gene. Germline RET mutations are associated with the autosomal-dominant inherited multiple endocrine neoplasia (MEN) 2A and 2B syndromes and the isolated familial medullary thyroid cancer syndrome. More than 100 RET codon mutations have been reported to date, with genotype–phenotype correlations that include the extent and aggressiveness of the medullary thyroid cancer and the presence of other features of the MEN2 syndromes. The latter include pheochromocytoma–paraganglioma, hyperparathyroidism, cutaneous lichen amyloidosis, and Hirschsprung disease. In this narrative review, we focus on RET proto-oncogene physiology and pathogenesis induced by germline and somatic RET mutations, the genotype–phenotype correlation, and the management and follow-up of patients with germline-mutated medullary thyroid cancer.