RELEVANCE OF RET PROTOONCOGENE MUTATIONS IN SPORADIC MEDULLARY-THYROID CARCINOMA

Analysis of peripheral blood or tumor DNA samples from 101 patients wi th apparent sporadic medullary thyroid carcinoma (MTC) was performed t o assess the frequency of RET proto-oncogene mutations in this patient population. Peripheral blood and/or tumor DNA was amplified by polyme rase chain reaction. DNA sequence or restriction enzyme analysis was p erformed to detect mutations of RET proto-oncogene codons 609, 611, 61 8, 620, 634, 768, and 918. Six of 101 patients with apparent sporadic MTC had peripheral blood DNA mutations more commonly associated with h ereditary MTC. In 4 patients, these mutations led to the identificatio n of previously unrecognized kindreds. The remaining 2 patients were e xamples of de novo mutations, A codon 918 mutation was found in 14 of 57 (similar to 25%) tumor DNA samples. Mutations were not identified i n the remaining patients. In this large cancer center population, simi lar to 6% of patients with sporadic MTC carry peripheral blood DNA mut ations, either inherited or de novo, more commonly associated with MEN 2A or familial MTC. Seven additional gene carriers were identified as a direct result of these studies, a 2-fold multiplying effect. We con clude routine application of RET proto-oncogene testing should be incl uded in all cases of apparent sporadic MTC.