ANALYSIS OF THE RET PROTOONCOGENE IN SPORADIC PARATHYROID ADENOMAS

Missense germline mutations of the RET proto-oncogene have recently be en identified in the hereditary cancer syndromes MEN2A, MEN2B, and FMT C, all characterized by medullary carcinoma, but also including phaeoc hromocytoma in MEN2A and MEN2B and parathyroid disease in MEN2A, In ad dition, somatic RET proto-oncogene mutations have been identified in a subset of sporadic medullary carcinomas and phaeochromocytomas. This study investigated the possibility that RET plays a role in sporadic p arathyroid neoplasia, Firstly, normal and neoplastic parathyroid tissu es were screened for expression of the RET proto-oncogene, using an RT -PCR approach on autopsy material. Secondly, 20 archival parathyroid a denomas were screened for somatic mutations in the transmembrane regio n of RET, the region associated with germline mutations in MEN2A and h ence parathyroid disease, using a PCR-solid phase direct sequencing ap proach, RET expression was identified in all the parathyroid tissues a nalysed, However, no mutations were identified in any of the 20 adenom as, suggesting either that other mechanisms of RET activation occur, s uch as translocation, or that RET plays a more minor role in the growt h control of the parathyroid cells than in C cells or phaeochromocytes .