Medullary carcinoma of the thyroid (MTC) is a rare tumour which occurs in both sporadic and hereditary forms. Mutations of the RET proto-oncogene have been identified in hereditary forms. The aim of our study was to confirm or exclude familial disease by examining for germline mutations in the RET proto-oncogene in patients with medullary thyroid carcinoma. Nine patients with medullary thyroid carcinoma and 4 of their children were studied. Peripheral blood was used to examine for mutations in the RET proto-oncogene. When this was not available, archival thyroid tissue was used. Seven patients had clinically sporadic tumours confirmed by mutational analysis of RET. Four children were at risk of being carriers of a mutated gene, as their fathers had histologically proven MTC and had tested positive for the mutation at codon 618 on exon 10 of the RET proto-oncogene. Three of these children carried the 618 mutation. To date, 2 have had a prophylactic thyroidectomy, the pathology of which revealed C-cell hyperplasia. One child had familial disease excluded by mutational analysis. One patient had a clinical diagnosis of MEN2B confirmed by detection of the 918 mutation on exon 16 of the RET proto-oncogene. RET proto-oncogene analysis is a reliable method of differentiating familial from sporadic MTC. Mutational information determines which family members of affected kindreds are at risk of developing the disease and can be used to affect clinical management.
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