副甲状腺機能亢進症 : 顎腫瘍症候群

The hyperparathyroidism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder characterized by the occurrence of parathyroid tumors in association with ossifying fibromas of the maxilla and/or mandible. HPT-JT-associated primary hyperparathyroidism is usually caused by a single parathyroid adenoma. Ossifying fibroma occurs in about 30% of individuals with HPT-JT syndrome. Many patients with HPT-JT syndrome present with a single benign parathyroid tumor; however, the optimal surgical approach to primary hyperparathyroidism has not yet been established. The gene responsible for HPT-JT syndrome on 1q31.2, known as CDC73 (formerly known as HRPT2), was identified and encodes a 531-amino acid protein known as parafibromin. Germline CDC73 mutations are detected in patients with HPT-JT syndrome, and majority (>75%) of mutations predict premature truncation of the parafibromin, and the demonstration of loss of heterozygosity at the CDC73 locus in tumors is consistent with a tumor suppressor role. Approximately 20% of patients with apparently sporadic parathyroid cancer are found to have germline CDC73 mutations, suggesting that such cases may, in fact, represent undiagnosed HPT-JT syndrome. Parafibromin is known to act as a tumor suppressor that inhibits expression of cyclin D1 and c-myc by recruiting histone methyltransferase. On the other hand, parafibromin can act in the opposing direction by binding β-catenin, thereby activating oncogenic Wnt signaling. Furthermore, parafibromin acts as a positive regulator of cell growth similar to an oncoprotein in the presence of SV40 large T antigen. These results suggest the context-dependent oncogenic or tumor- suppressor functions of parafibromin.