1. Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study
- Author
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Léa Maria Zanini Maciel, Carla Vaz Ferreira, Sergio P. A. Toledo, Flávia O. F. Valente, Luciana A. Castroneves, Rui M. B. Maciel, Gisah Amaral de Carvalho, Rita V Weiss, Janete M. Cerutti, Henrique de Campos Reis Galvão, Tânia M B L Ferraz, Célia Regina Nogueira, Patrícia Künzle Ribeiro Magalhães, Francisco M de Castro, Shana de Souto Weber, Vera L.G. Leal, Cencita H. C. N. Pessoa, M Inez C França, Natassia Elena Bufalo, Gláucia Maria Ferreira da Silva Mazeto, Maria A. Sousa, Ji H. Yang, Bibiana Prada, Débora Rodrigues Siqueira, M Cecília Martins-Costa, Magnus R. Dias-da-Silva, Rossana Corbo, João Roberto Maciel Martins, Ana Luiza Maia, Ana O. Hoff, Delmar M. Lourenço, Laura Sterian Ward, Edenir Inêz Palmero, Hans Graf, Marcio W Lauria, Rodrigo A. Toledo, Alexander A. L. Jorge, Ligia V. M. Assumpção, Anelise I Impellizzeri, Ilda S. Kunii, Fernanda Vaisman, Lucieli Ceolin, Fausto Germano-Neto, André Lopes Carvalho, Susan C. Lindsey, and Cleber P. Camacho
- Subjects
Genetics ,lcsh:RC648-665 ,business.industry ,Endocrinology, Diabetes and Metabolism ,Research ,Medullary thyroid cancer ,Multiple endocrine neoplasia type 2 ,Disease ,medicine.disease ,Genome ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,pheochromocytoma ,Thyroid carcinoma ,Exon ,Endocrinology ,Germline mutation ,Genotype-phenotype distinction ,medullary thyroid carcinoma ,Internal Medicine ,medicine ,multiple endocrine neoplasia ,business ,RET ,Brazil - Abstract
Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome.
- Published
- 2019