Clinical Science- THE MUTATIONS OF RET PROTO-ONCOGENE INMEDULLARYTHYROID CARCINOMAS IN IRAN

Medullary thyroid carcinoma (MTC) occurs both sporadically and in the autoso-mal dominantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes. The distinction between true sporadic MTC and a new mutation familial case is important for future clinical management of both the patient and family.The susceptibility gene for hereditary MTC is the RET proto-oncogene. DNA analysis for germline mutations of the RET proto-oncogene was performed in a series of 24 patients with MTC [appar-ently sporadic MTC (20 cases), familial MTC (2 cases), MEN 2A (one case) and MEN 2B (one case)] to determine whether they were true sporadic cases or heredi-tary forms. Genomic DNA was amplified using polymerase chain reaction (PCR) and oligonucleotide primers for exons 10 & 11. The PCR products were examined by restriction enzymes analysis to detect the mutations. One of the 20 patients with appar-ent sporadic MTC had exon 10 mutation (Cys-620 Arg); and exon 11 mutation (Cys-634 Trp) was also found in the index case with MEN 2A. No mutation was detected in the other patients. Three of six evaluated members of the MEN 2A patient had the same mutation. We conclude that routine application of RET proto-oncogene testing should be included in all cases of apparent sporadic MTC.