title: Clinical and molecular genetics of parathyroid neoplasms.
abstract: Primary hyperparathyroidism (HPT) results from the excessive secretion of parathyroid hormone from parathyroid tumours. While most HPT is sporadic, it is associated with a familial syndrome in a minority of cases. The study of these syndromes has helped define the pathophysiology of both familial and sporadic parathyroid neoplasms. Investigation of kindred with multiple endocrine neoplasia type 1 (MEN1) and the hyperparathyroidism-jaw tumour syndrome (HPT-JT) led to the discovery of the tumour suppressor genes MEN1 and HRPT2. We now recognise that somatic mutations in MEN1 and HRPT2 tumour suppressor genes are frequent events in sporadic parathyroid adenomas and carcinomas, respectively. Parathyroid tumours in the MEN2A syndrome result from mutational activation of the RET oncogene. The CCND1/PRAD1 oncogene was discovered by analysis of sporadic parathyroid tumours. Studies of familial isolated HPT and analysis of chromosomal loss and gain in parathyroid tumours suggest that other genes relevant to parathyroid neoplasia await identification.
authors.affiliation: Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 10 Room 8C-101, 10 Center Dr. MSC 1752 Bethesda, MD 20892-1752, USA. sharrettsj@niddk.nih.gov
authors.forename: John M
authors.initials: JM
authors.lastname: Sharretts
authors.forename: William F
authors.initials: WF
authors.lastname: Simonds
mesh_terms: D005260:Female; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000235:genetics* / Q000473:pathology; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics / Q000473:pathology; D010281:Parathyroid Hormone / Q000235:genetics; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C454900:CDC73 protein, human; D010281:Parathyroid Hormone; D025521:Tumor Suppressor Proteins; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human