A primer on the genetics of medullary thyroid cancer

摘要

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 mutation; 43%–65% of sporadic cases harbour a somatic event in the gene. Germline mutations are associated with the autosomal-dominant inherited multiple endocrine neoplasia ( ) 2 and 2 syndromes and the isolated familial medullary thyroid cancer syndrome. More than 100 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 2 syndromes. The latter include pheochromocytoma–paraganglioma, hyperparathyroidism, cutaneous lichen amyloidosis, and Hirschsprung disease.