1. Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study.
- Author
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Maciel RMB, Camacho CP, Assumpção LVM, Bufalo NE, Carvalho AL, de Carvalho GA, Castroneves LA, de Castro FM, Ceolin L, Cerutti JM, Corbo R, Ferraz TMBL, Ferreira CV, França MIC, Galvão HCR, Germano-Neto F, Graf H, Jorge AAL, Kunii IS, Lauria MW, Leal VLG, Lindsey SC, Lourenço DM, Maciel LMZ, Magalhães PKR, Martins JRM, Martins-Costa MC, Mazeto GMFS, Impellizzeri AI, Nogueira CR, Palmero EI, Pessoa CHCN, Prada B, Siqueira DR, Sousa MSA, Toledo RA, Valente FOF, Vaisman F, Ward LS, Weber SS, Weiss RV, Yang JH, Dias-da-Silva MR, Hoff AO, Toledo SPA, and Maia AL
- 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
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