SFEBES2007 Poster Presentations Thyroid (51 abstracts)
Several RET proto-oncogene germline mutations with dominant inheritance, predispose to hereditary medullary thyroid carcinoma (MTC), and whether the MTC is sporadic or hereditary should be determined by a direct analysis of the RET proto-oncogene. 85% of MEN IIA patients and 30% of patients with familial medullary thyroid carcinoma have mutations at codon 634 (exon 11). In 88 consecutive patients with MTC, the characterization of RET mutations in exon 11 had been done by PCR with restriction fragment length polymorphism analysis, and by sequencing of purified PCR products on AFLexpress II using Thermo Sequenase Cy5 Terminator Cycle Sequencing Kit (Amersham Biosciences). We found three different mutations in RET proto-oncogene exon 11 (codon 634): 1) TGC to CGC with cysteine substituted for an arginine in 18 (20%) patients. Only 7 patients (8%) had de novo mutation while other mutations were hereditary. 2) TGC to TAC with cysteine substituted for tyrosine in 4 patients (4%). Only one patient had de novo mutation; and 3) TGC to TTC with cysteine substituted for phenylalanine in 3 patients (3%).
Genetic screening in patients with MTC should be performed routinely in specialized centers in order to identify index-cases of hereditary forms of MTC and govern further familial screening for preclinical disease.