GERMLINE DINUCLEOTIDE MUTATION IN CODON-883 OF THE RET PROTOONCOGENE IN MULTIPLE-ENDOCRINE-NEOPLASIA TYPE-2B WITHOUT CODON-918 MUTATION

The autosomal dominant multiple endocrine neoplasia type 2 syndromes ( MEN 2) comprise three clinically distinct entities, MEN 2A, familial m edullary thyroid carcinoma and MEN 2B, which share a common clinical f eature: medullary thyroid carcinoma (MTC). MEN 2B is considered to hav e the most aggressive form of MTC. Therefore, early detection of MEN 2 B in order to prevent potentially lethal MTC is important. More than 9 5% of all MEN 2B cases are caused by germline mutation at codon 918 (M 918T) in exon 16 of the RET proto-oncogene. In this study, we demonstr ate the presence of germline codon 883 mutation (A883F) in 2 of 3 unre lated MEN 2B cases without codon 918 mutation. Our data demonstrate a novel etiologic event which may have roles in predisposition to MEN 2B when present in the germline and in the pathogenesis of sporadic MTC when somatic.