Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study

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Maciel, Rui M. B. ; Camacho, Cleber P. ; Assumpcao, Ligia V. M. ; Bufalo, Natassia E. ; Carvalho, Andre L. ; de Carvalho, Gisah A. ; Castroneves, Luciana A. ; de Castro Jr, Francisco M. ; Ceolin, Lucieli ; Cerutti, Janete M. ; Corbo, Rossana ; Ferraz, Tania M. B. L. ; Ferreira, Carla, V ; Franca, M. Inez C. ; Galvao, Henrique C. R. ; Germano-Neto, Fausto ; Graf, Hans ; Jorges, Alexander A. L. ; Kunii, Ilda S. ; Lauria, Marcio W. ; Leal, Vera L. G. ; Lindsey, Susan C. ; Lourenco Jr, Delmar M. ; Mader, Lea M. Z. ; Magalhaes, Patricia K. R. ; Martins, Joao R. M. ; Cecilia Martins-Costa, M. ; Mazetor, Glaucia M. F. S. ; Impellizzeri, Anelise I. ; Nogueira, Celia R. ; Palmero, Edenir, I ; Pessoa, Cencita H. C. N. ; Prada, Bibiana ; Siqueira, Debora R. ; Sousa, Maria Sharmila A. ; Toledo, Rodrigo A. ; Valente, Flavia O. F. ; Vaisman, Fernanda ; Ward, Laura S. ; Weber, Shana S. ; Weiss, Rita, V ; Yang, Ji H. ; Dias-da-Silva, Magnus R. ; Hoff, Ana O. ; Toledo, Sergio P. A. ; Maia, Ana L.

• Document type: Journal article
• Source: ENDOCRINE CONNECTIONS; v. 8, n. 3, p. 10-pg., 2019-03-01.

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 Brazili an 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. (AU)

• FAPESP's process: 13/01476-9 - Screening of variants of unkown significance (VUS) in the RET proto-oncogene in patients with multiple endocrine neoplasia type 2 and healthy individual controls
• Grantee: Sergio Pereira de Almeida Toledo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/06570-6 - Comprehensive whole exome, paired-end RNA and genome sequencing: new insights into genetic bases of thyroid carcinoma in pediatric and adult ages and applications in clinical practice
• Grantee: Janete Maria Cerutti
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/21942-1 - Perceptions and attitudes of patients, relatives, health professionals and regulators on bioethical issues in Brazil and the United Kingdom: the case study of the familial medullary thyroid carcinoma
• Grantee: Maria Sharmila Alina de Sousa
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 06/60402-1 - Medular carcinoma of the thyroid: revisiting the clinical, molecular biological, biochemical and biological aspects following findings of molecular genetics
• Grantee: Rui Monteiro de Barros Maciel
• Support Opportunities: Research Projects - Thematic Grants