MUTATION OF RET CODON-768 IS ASSOCIATED WITH THE FMTC PHENOTYPE

Multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B), and f amilial medullary thyroid carcinoma (FMTC) are inherited cancer syndro mes resulting from mutations in the RET proto-oncogene. Missense mutat ions of five codons in exons 10 and 11 are found in both MEN 2A and FM TC families, while mutations at codon 768 in exon 13 have been identif ied in three FMTC families. We report here the results of mutation ana lysis on a large multi-generation family with multiple cases of medull ary thyroid carcinoma (MTC) or C-cell hyperplasia and two individuals with isolated adrenal medullary hyperplasia. A mutation in exon 13, wh ich alters codon 768 from a GAG (Glu) to a GAC (Asp), was found to seg regate with the FMTC phenotype in this family but not with the adrenal medullary hyperplasia. These findings suggest that the codon 768 muta tion does not predispose to adrenal medullary hyperplasia, but is an a ccurate predictor of the MTC phenotype in this family.