ANALYSIS OF RET PROTOONCOGENE ABNORMALITIES IN PATIENTS WITH MEN 2A, MEN 2B, FAMILIAL OR SPORADIC MEDULLARY-THYROID CARCINOMA

Medullary thyroid carcinoma (MTC) may occur either as a sporadic or fa milial (FMTC) disease. Multiple endocrine neoplasia (MEN) type 2, inhe rited as an autosomal dominant disease, is characterized by coexistenc e of MTC with other endocrine neoplasia. Activating mutations of the R ET proto-oncogene, involving the somatic or the germinal cell lineage, are found in both inherited and acquired forms. In this study, RET mu tations were screened in 47 individuals either affected by MTC or belo nging to families with hereditary MTC. Exons 10, 11, 13, 14, 15 and 16 of the RET gene were amplified by polymerase chain reaction and exami ned by DNA sequence and/or restriction enzyme analysis to detect mutat ions in purified amplicons. Six MEN 2A families with a germline mutati on at codon 634, one FMTC family carrying a mutation at codon 618 and two MEN 2B families with a mutation at codon 918 were identified. In a ffected members of a MEN 2A family no known RET mutations were observe d. Besides, we identified a germline mutation in a patient with appare ntly sporadic MTC and in two out of three sons, indicating the presenc e of a sporadic misclassified familial disease. In all of the families examined we were able to distinguish the affected vs unaffected (not at risk) members. A somatic mutation of codon 918 was detected in thre e out of ten patients with apparently sporadic MTC. (J. Endocrinol. In vest. 21: 358-364, 1998) (C)1998, Editrice Kurtis.