SOMATIC MUTATIONS IN THE RET-PROTOONCOGEN E IN PATIENTS WITH SPORADICMEDULLARY-THYROID CARCINOMA

Medullary thyroid carcinoma (MTC) occurs sporadically or as apart of i nherited cancer syndrome, multiple endocrine neoplasia type 2A or 2B ( MEN 2A or 2B). Germline mutations has been identified in cystein codon s within exon 10, 11 and 13 for MEN 2A and familial medullary thyroid carcinoma (FMTC), whereas in MEN 2B mutation has been determinated exc lusively in exon 16, the catalytic core region of the tyrosine kinase domain. To determinate if RET mutations similar to those in MEN 2A and 2B play a role in the carcinogenesis of sporadic MTC, we analysed 20 sporadic medullary carcinomas for somatic mutations in exon 10, 11 and 16 using PCR, Single Stranded Comfortional Polymorphism (SSCP) and no nradioactve sequencing. We found that 33% of sporadic MTC had MEN 2B s pecific mutations in codon 918 in exon 16, whereas in none of the tumo rs mutations in exon 10 and 11 were detectable. This findings allow to discriminate between ''truely'' sporadic and ''apparently'' sporadic MTC, that are index cases of new MEN 2/FMTC families.