SOMATIC RET PROTOONCOGENE MUTATIONS IN SPORADIC C-CELL CARCINOMA OF THE THYROID

Germline mutations of the RET proto-oncogene localized on chromosome 1 0q11.2 are the underlying cause of hereditary medullary thyroid carcin oma. In MEN 2A and FMTC, mutations can be found in exons 10, 11, 13 or 14. MEN 2B is characterized by a specific mutation in exon 16. In a s ignificant number of sporadic MTC somatic mutations in codon 918 (exon 16) are detectable. Some rare sporadic MTC present somatic mutations in codons 611, 634, 768 and 883. Recently, deletion-insertion of the R ET proto-oncogene in exon 11 and a deletion in exon 10 has been found. RET proto-oncogene mutations are not only responsible for the develop ment of the familial MTC, but may also play an important role in the p athogenesis of sporadic MTC. However, the prognostic relevance of thes e somatic events is still unclear.