Abstract 14

RET proto-oncogen mutation results in a dominant autosomic inherited syndrome (MEN 2) presenting three distinct subtypes: MEN 2A, MEN 2B and familial medullary thyroid carcinoma (FMTC). Detection of RET proto-oncogen mutation is a predictor before clinical or biochemical evidence of the disease is present and leads to preventive thyroid removal since there is no effective treatment for metastases. The aim of the present study was to characterize mutations in the RET proto-oncogen in affected patients and to identify potentials carriers in their families. Two families with FMTC (5 and 6 members), 4 with MEN 2A (5, 5, 4, and 3 members) and 2 with MEN 2B (5 and 1 members), were studied. PCR amplification was performed using specific primers for exons 10, 11, and 16, followed by direct sequencing. Mutations at codon 634 in exon 11 were found in 15 subjects with FMTC and MEN 2 A. TGC → CGC (cysteine to arginine) in 9 cases. TGC → TAC (cysteine to tyrosine) in 3, and TGC → TTC (cysteine to phenilalanine) in 3. A unique mutation at codon 918 in exon 16, ATG → ACG (methionine to threonine), was found in both MEN 2 B affected patients. RET mutations were detected in all affected patients, confirming the diagnosis, and in 9 members of their families. In four of the carriers total thyroidectomy was performed. Anatomopathological study showed C-cells hyperplasia or in-situ microcarcinoma in two children (9 and 12 y) with no clinical signs of disease and medullary thyroid carcinoma in two adults (36 and 40 y) who were previously unaware of the presence of thyroid nodules. The early detection of RET mutation followed by total thyroidectomy may prevent the development of the disease, specially at pediatric age, and avoid the fatal outcome of delayed medullary thyroid carcinoma diagnosis.