Estudo de familias com neopastia endocrina multipla tipo 2A, 2B e carcinoma medular familiar: correlação genotipo, fenótipo e isoformas da proteína RET (RET 9 e RET 51)

Abstract

The multiple endocrine neoplasia Type 2 (MEN-2) is a hereditary syndrome comprising: medullary thyroid carcinoma (MTC), primary hyperparathyroidism, pheochromocytoma and other non-endocrine diseases. Is subdivided into three phenotypic related disorders: MEN-2A, MEN-2B and familial medullary thyroid carcinoma (FMTC). The MEN-2A comprises MTC (95% to 100% of cases), pheochromocytoma (30% to 50%) and parathyroid hyperplasia (10% to 30%). The MEN-2B presents MTC (95% to 100%), pheochromocytoma (30% to 50%), ganglioneuromatosis of the gastrointestinal tract, and an asthenic "Marfanoid" body habitus. in 100% of cases. The MEN-2 is associated with mutations in proto-oncogene RET (10q11), which determine the standing of the RET receptor activation. The protooncogene RET gene encodes around 10 isoformas, and isoformas RET 9 and RET 51, the most important in the development of MEN-2. For the determination of correlation genotype-phenotype and isoformas protein RET (RET 9, RET 51 and residue Tyr Y1062) were studied 58 individuals resident in the State of Minas Gerais (33 cases of MTC isolated and 25 family). Were used genetic sequencing techniques of peripheral blood and immunohistochemistry of paraffin blocks from surgical treatment that hadundergone patients. The most prevalent phenotype was FMTC and mutation observed was the L790F. Twenty-three patients presented the SNP L790F, six SNPG691S patients and four patients the SNP A764A, not reported in the literature. The small number of patients with MEN-2 from whom the paraffin blocks were obtained has not allowed the interpretation of the correlation between genotype and phenotype, and theexpression of isoformas protein ret. The work has relevance clinical and laboratory for being the first attempt to research and patient record with CMT sporadic and CMT family (MEN-2) in the State of Minas Gerais.