Frequency of hereditary medullary thyroid Carcinoma and RET proto-oncogen polymorphisms in patients with apparently sporadic medullary thyroid carcinoma

DRA GABRIELA SANSO; DRA ANA VIEITES; DRA GLORIA LEVIN; DRA MARTA BARONTINI

Nueva York

Congreso; XXI REUNION DE LA SOCIEDAD LATINOAMERICANA DE ENDOCRINOLOGIA PEDIATRICA; 2009

SLEP

Medullary thyroid carcinoma (MTC) originates from C cells of the thyroid and represents approximately 10% of all thyroid cancers. Approximately 75% of all MTCs are believed to be sporadic, whereas the remaining 25% correspond to inherited cancer syndromes. Little is known about the etiology of sporadic MTC although previous reports suggest that the presence of inherited genetic variants of RET are associated with the predisposition to development of sporadic MTC. Several single nucleotide polymorphisms of the RET gene have been described in the general population as well as in patients with MTC. Aim: to evaluate the incidence of hereditary disease in patients with apparently sporadic MTC and to describe the frequency of inherited genetic variants in the RET proto-oncogen. Patients and Methods: Screenig of Ret exons 10, 11, 13, 14 and 15 was performed by direct sequencing of DNA from 74 patients with apparently sporadic MTC. The frequency of Leu769Leu (exón 13), Ser 804Ser (exón 14) Ser904Ser (exón 15) and Gly691Ser (exón 11) polymorphisms was studied in 36 of them. Results: 4/74 patients (5.4%) with apparently sporadic MTC presented hereditary disease. The mutations found were: Cys620Arg (2), Cys618Phe (1) and Cys634Tyr (1). 13/39 relatives (9> 20y and 4< 20y) were studied. In seven of them the ret mutation was detected. 36/74 patients were studied for polymorphisms and the allelic frequencies were: 44.4% (16/36) Leu769Leu, 2 homozygous and 14 heterozygous, 33.3% (12/36) Ser904Ser, 2 homozygous and 10 heterozygous, 50% (8/16) Gly691Ser, 3 homozygous and 5 heterozygous. All patients were negative for Ser836Ser. Conclusions: The frequency of inherited disease that we found among patients with apparent sporadic MTC strengthens the routine application of Ret proto-oncogen DNA screening in all cases of this disease. The frequency of RET polymorphisms detected in these patients may suggest a potential role of these variants in the development of sporadic MTC. A putative role of the polymorphism as genetic modifier remains to be established and further studies are necessary to characterize the clinical behavior of MTC.