A NOVEL SOMATIC MUTATION IN THE RET PROTOONCOGENE IN FAMILIAL MEDULLARY-THYROID CARCINOMA WITH A GERMLINE CODON-768 MUTATION

In individuals who carry germline mutations in tumor suppressor genes predisposing them to inherited cancer syndromes, occurrence of somatic mutations in the same genes contributes to tumorigenesis. Germline mu tations in the RET proto-oncogene predispose individuals to multiple e ndocrine neoplasia (MEN) type 2 syndromes, Since these mutations are o ncogenic by themselves, somatic mutations in the same gene had been th ought unnecessary, Recently, a somatic mutation at codon 918 of RET wa s reported in medullary thyroid carcinoma (MTC) and C-cell hyperplasia in patients with MEN 2A or familial MTC (FMTC), suggesting its possib le contribution to tumorigenesis. We describe here a novel somatic mut ation at codon 919 in a patient with FMTC carrying a germline mutation at codon 768 that may also be related to tumor progression.