Table 1.

Genes implicated in syndromic and sporadic parathyroid tumorigenesis, and related syndromes

Gene	Protein encoded	Associated hyperparathyroid syndrome: main syndromic manifestations	Features of syndromic parathyroid tumors	Defect in sporadic parathyroid tumors
MEN1	Menin	Multiple endocrine neoplasia type 1: anterior pituitary, parathyroid, enteropancreatic, foregut carcinoid tumors	Multiple, asymmetric tumors typical (> 99% benign)	Inactivation in ~25- 35% of benign tumors; mutation exceedingly rare in cancer
HRPT2/CDC73	Parafibromin	Hyperparathyroidism-jaw tumor syndrome: fibro-osseous jaw, parathyroid, uterine tumors; renal cysts	Single tumor common (~15% malignant)	Inactivation in ~70% of cancers; mutation rare in sporadic adenomas
CASR	Calcium- sensing receptor	Familial hypocalciuric hypercalcemia (FHH) with heterozygous inactivation; neonatal severe hyperparathyroidism (NSHPT) with homozygous inactivation	FHH: near-normal size and surgical pathology; altered serum calcium set-point for PTH release NSHPT: Marked enlargement of multiple glands	Decreased expression common; mutation exceedingly rare
RET	c-Ret	Multiple endocrine neoplasia type 2A: medullary thyroid cancer, pheochromocytoma, parathyroid tumors	Single tumor common (> 99% benign)	Mutation exceedingly rare
CCND1/PRAD1	Cyclin D1	NA	NA	Overexpression results from DNA rearrangement involving PTH gene

NA, not applicable