Primary hyperparathyroidism (HPT) is a common endocrine disorder that can cause significant morbidity. HPT may be due to benign neoplasia of a single parathyroid gland (adenoma), benign neoplasia involving multiple parathyroid glands (hyperplasia), and rarely, to malignant neoplasia of a parathyroid gland (carcinoma). The etiology of parathyroid neoplasia has not been defined, but clinical and epidemiologic studies indicate that hyperplasia is often due to an inherited defect (multiple endocrine neoplasia types 1 and 2), and that a history of head and neck irradiation is associated with a significantly higher risk of developing parathyroid neoplasia. As with other forms of neoplasia, parathyroid tumors are presumably due to inherited (germ-line mutation) and/or acquired (somatic mutation) defects in specific genes. Etiologic genetic defects could include inappropriate expression of transforming """"""""oncogenes"""""""" and/or loss of expression of tumor """"""""suppressor"""""""" genes. The availability of surgically resected parathyroid tumors allows us to search for tumor-specific genetic abnormalities that may be involved in development of parathyroid neoplasia. We have found rearrangement of the parathyroid hormone gene in only 1 of 43 parathyroid adenomas, but this gene abnormality may be pathogenetically relevant. In contrast, point mutations in ras oncogenes were not found in any parathyroid tumors. In both """"""""hyperplastic"""""""" glands from subjects with MEN I and in sporadic adenomas loss of heterozygosity for loci on chromosome 11q13 was found. The data show that tumors in MEN I are monoclonal, and that a locus in 11q13 may encode a tumor """"""""suppressor"""""""" gene.
