Medullary thyroid carcinoma (MTC) occurs usually in sporadic form, but about a quarter of the cases are hereditary and appear as part of one of the multiple endocrine neoplasia type 2 (MEN2) syndromes. Mutations in the RET protooncogene are known to be the cause of the MEN2A and familial medullary thyroid carcinoma (FMTC) syndromes in the majority of the families. Direct DNA testing allows prophylactic thyroidectomy to be offered to individuals carrying a mutation in the above codons, and in mutation-negative cases it reduces the yearly screening-related burden on family members at risk of the disease. By DNA sequencing and PCR-restriction fragment length polymorphisms, 65 MTC probands were examined for mutations in residues 609, 611, 618, 620 of exon 10, and in residues 634, 768, 804 of exons 11, 13, and 14 respectively of the RET protooncogene. In our study, mutations in the above codons were detected in all of the 14 clinically MEN2A and FMTC families. One of these mutations, TGC609 TCC has not been reported previously. Of the 14 probands with the mutation, 25 relatives also had the identified mutation and 18 relatives proved to be non-carriers. Among the 51 probands with clinically sporadic MTC, none was found to carry a mutation in the above positions even if indirect signs of MTC, pheochromocytoma or hyperparathyroidism could be detected in some families. The frequency of the TGC634AGC mutation is unexpectedly high in our samples, which can probably be attributed to a founder effect. We conclude that screening for mutations in these codons is effective in families fulfilling the strict clinical criteria of MEN2A or FMTC.

This article has been cited by other articles:

				S Jindrichova, J Vcelak, P Vlcek, M Neradilova, J Nemec, and B Bendlova Screening of six risk exons of the RET proto-oncogene in families with medullary thyroid carcinoma in the Czech Republic J. Endocrinol., November 1, 2004; 183(2): 257 - 265. [Abstract] [Full Text] [PDF]

				K. E. Kruckeberg and S. N. Thibodeau Pyrosequencing Technology as a Method for the Diagnosis of Multiple Endocrine Neoplasia Type 2 Clin. Chem., March 1, 2004; 50(3): 522 - 529. [Abstract] [Full Text] [PDF]

				M. K. Punales, H. Graf, J. L. Gross, and A. L. Maia RET Codon 634 Mutations in Multiple Endocrine Neoplasia Type 2: Variable Clinical Features and Clinical Outcome J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2644 - 2649. [Abstract] [Full Text] [PDF]

				P. Igaz, A. Patocs, K. Racz, I. Klein, A. Varadi, and O. Esik Occurrence of Pheochromocytoma in a MEN2A Family with Codon 609 Mutation of the RET Protooncogene J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2994 - 2994. [Full Text] [PDF]