Endocrine Abstracts (2006) 11 P512

Mutation at codon 804 detected in a Greek kindred by screening of the RET gene in patients with medullary thyroid carcinoma

N Mytakidis1, E Vassiliou1, V Liakos1, L Papagrigoriou1, F Hadzimarkou1, I Kostoglou-Athanasiou1, G Koutsodontis3, A Ladopoulou3, T Bei3, D Yannoukakos2 & P Kaldrymidis1

1Department of Endocrinology, Metaxa Hospital, Piraeus, Greece; 2Molecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research “Demokritos”, Athens, Greece; 3BioGenomica, Center for Genetic Research & Analysis, Athens, Greece.

Medullary Thyroid Carcinoma (MTC) is a rare cancer that arises from the thyroid C-cells and occurs as sporadic in 75% of the cases. In 25% of MTC cases, mutations of the RET proto-oncogene are responsible for the development of three dominantly inherited neoplastic disorders including multiple endocrine neoplasia (MEN) 2A, MEN 2B and familial medullary thyroid carcinoma (FMTC). Since 2–8% of MTC cases considered sporadic conceal germline mutations, direct analysis of the RET gene should be performed in all MTC patients.

In this study we have analysed RET gene for mutations in 30 Greek patients, belonging in unrelated families, who had previously undergone surgery for sporadic MTC. Informed consent was obtained and exons 10, 11, 13, 14, 15 and 16 were screened in all of the patients. A 51-years-old female patient carrying the mutation V804L was identified. Genetic testing in 6 members of her family revealed the presence of 3 more heterozygote carriers without clinical symptoms. The index-patient’s mother refused surgery. Her 31-years-old son underwent prophylactic surgery and diffuse C-cell hyperplasia has been detected. His 4-years-old son is a mutation carrier too. All mutation carriers do not present any clinical and laboratory evidence of pheochromocytoma and primary hyperparathyroidism. The index-patient, 2 years after surgery, is still without evidence of MTC, as assessed with pentagastrin stimulated calcitonin levels.

Two types of mutations have been observed in codon 804: V804L and V804M. Presently the V804M mutation has been associated only with FMTC, whereas pheochromocytoma has been reported in a family with the V804L mutation. There is wide clinical variability and there is not yet agreement as to therapeutic strategies for mutation carriers. We recommended annual evaluation for both adult patients with PTH, calcium and metanephrines; additionally a pentagastrin stimulation test every two years for the child.