Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study
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 accord...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Bioscientifica
2019-03-01
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| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/8/3/EC-18-0506.xml |
| _version_ | 1818197906006474752 |
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| author | Rui M B Maciel Cleber P Camacho Lígia V M Assumpção Natassia E Bufalo André L Carvalho Gisah A de Carvalho Luciana A Castroneves Francisco M de Castro Jr Lucieli Ceolin Janete M Cerutti Rossana Corbo Tânia M B L Ferraz Carla V Ferreira M Inez C França Henrique C R Galvão Fausto Germano-Neto Hans Graf Alexander A L Jorge Ilda S Kunii Márcio W Lauria Vera L G Leal Susan C Lindsey Delmar M Lourenço Jr Léa M Z Maciel Patrícia K R Magalhães João R M Martins M Cecília Martins-Costa Gláucia M F S Mazeto Anelise I Impellizzeri Célia R Nogueira Edenir I Palmero Cencita H C N Pessoa Bibiana Prada Débora R Siqueira Maria Sharmila A Sousa Rodrigo A Toledo Flávia O F Valente Fernanda Vaisman Laura S Ward Shana S Weber Rita V Weiss Ji H Yang Magnus R Dias-da-Silva Ana O Hoff Sergio P A Toledo Ana L Maia |
| author_facet | Rui M B Maciel Cleber P Camacho Lígia V M Assumpção Natassia E Bufalo André L Carvalho Gisah A de Carvalho Luciana A Castroneves Francisco M de Castro Jr Lucieli Ceolin Janete M Cerutti Rossana Corbo Tânia M B L Ferraz Carla V Ferreira M Inez C França Henrique C R Galvão Fausto Germano-Neto Hans Graf Alexander A L Jorge Ilda S Kunii Márcio W Lauria Vera L G Leal Susan C Lindsey Delmar M Lourenço Jr Léa M Z Maciel Patrícia K R Magalhães João R M Martins M Cecília Martins-Costa Gláucia M F S Mazeto Anelise I Impellizzeri Célia R Nogueira Edenir I Palmero Cencita H C N Pessoa Bibiana Prada Débora R Siqueira Maria Sharmila A Sousa Rodrigo A Toledo Flávia O F Valente Fernanda Vaisman Laura S Ward Shana S Weber Rita V Weiss Ji H Yang Magnus R Dias-da-Silva Ana O Hoff Sergio P A Toledo Ana L Maia |
| author_sort | Rui M B Maciel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T01:57:25Z |
| format | Article |
| id | doaj.art-37d0d78e06b24b48bb6c7725c95f14cc |
| institution | Directory Open Access Journal |
| issn | 2049-3614 2049-3614 |
| language | English |
| last_indexed | 2024-12-12T01:57:25Z |
| publishDate | 2019-03-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-37d0d78e06b24b48bb6c7725c95f14cc2022-12-22T00:42:18ZengBioscientificaEndocrine Connections2049-36142049-36142019-03-0183289298https://doi.org/10.1530/EC-18-0506Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN studyRui M B Maciel0Cleber P Camacho1Lígia V M Assumpção2Natassia E Bufalo3André L Carvalho4Gisah A de Carvalho5Luciana A Castroneves6Francisco M de Castro Jr7Lucieli Ceolin8Janete M Cerutti9Rossana Corbo10Tânia M B L Ferraz11Carla V Ferreira12M Inez C França13Henrique C R Galvão14Fausto Germano-Neto15Hans Graf16Alexander A L Jorge17Ilda S Kunii18Márcio W Lauria19Vera L G Leal20Susan C Lindsey21Delmar M Lourenço Jr22Léa M Z Maciel23Patrícia K R Magalhães24João R M Martins25M Cecília Martins-Costa26Gláucia M F S Mazeto27Anelise I Impellizzeri28Célia R Nogueira29Edenir I Palmero30Cencita H C N Pessoa31Bibiana Prada32Débora R Siqueira33Maria Sharmila A Sousa34Rodrigo A Toledo35Flávia O F Valente36Fernanda Vaisman37Laura S Ward38Shana S Weber39Rita V Weiss40Ji H Yang41Magnus R Dias-da-Silva42Ana O Hoff43Sergio P A Toledo44Ana L Maia45Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, BrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, BrazilFaculdade de Ciências Médicas, Universidade de Campinas, Campinas, São Paulo, BrazilFaculdade de Ciências Médicas, Universidade de Campinas, Campinas, São Paulo, BrazilHospital de Câncer de Barretos, Barretos, São Paulo, BrazilFaculdade de Medicina, Universidade Federal do Paraná, Curitiba, Paraná, BrazilFaculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil; Instituto do Câncer do Estado de São Paulo, São Paulo, São Paulo, BrazilUniversidade Federal do Ceará, Fortaleza, Ceará, BrazilHospital de Clínicas de Porto Alegre and Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, BrazilInstituto Nacional do Câncer, Rio de Janeiro, Rio de Janeiro, BrazilHospital Geral de Fortaleza, Fortaleza, Ceará, BrazilHospital de Clínicas de Porto Alegre and Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilUniversidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Hospital Santa Rita de Cássia, Vitória, Espírito Santo, BrazilHospital de Câncer de Barretos, Barretos, São Paulo, BrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, BrazilFaculdade de Medicina, Universidade Federal do Paraná, Curitiba, Paraná, BrazilFaculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, BrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, BrazilFaculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilInstituto Estadual de Diabetes e Endocrinologia, Rio de Janeiro, Rio de Janeiro, BrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, BrazilFaculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil; Instituto do Câncer do Estado de São Paulo, São Paulo, São Paulo, BrazilFaculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, BrazilFaculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, BrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, BrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil; Hospital Geral de Fortaleza, Fortaleza, Ceará, Brazil; Universidade de Fortaleza, Fortaleza, Ceará, BrazilFaculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, São Paulo, BrazilFaculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilFaculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, São Paulo, BrazilHospital de Câncer de Barretos, Barretos, São Paulo, Brazil; Faculdade de Ciências da Saúde de Barretos Dr. Paulo Prata, Barretos, São Paulo, BrazilInstituto Nacional do Câncer, Rio de Janeiro, Rio de Janeiro, BrazilFaculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, São Paulo, BrazilHospital de Clínicas de Porto Alegre and Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil; Escola Fiocruz de Governo, Fundação Oswaldo Cruz and Ministério da Saúde, Brasília, Distrito Federal, BrazilFaculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil; Vall d’Hebron Institute of Oncology (VHIO), CIBERONC, Barcelona, SpainEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, BrazilInstituto Nacional do Câncer, Rio de Janeiro, Rio de Janeiro, BrazilFaculdade de Ciências Médicas, Universidade de Campinas, Campinas, São Paulo, BrazilHospital de Clínicas de Porto Alegre and Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilInstituto Estadual de Diabetes e Endocrinologia, Rio de Janeiro, Rio de Janeiro, BrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, BrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, BrazilFaculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil; Instituto do Câncer do Estado de São Paulo, São Paulo, São Paulo, BrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil; Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, BrazilHospital de Clínicas de Porto Alegre and Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilMultiple 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.https://ec.bioscientifica.com/view/journals/ec/8/3/EC-18-0506.xmlRETBrazilmultiple endocrine neoplasiamedullary thyroid carcinomapheochromocytoma |
| spellingShingle | Rui M B Maciel Cleber P Camacho Lígia V M Assumpção Natassia E Bufalo André L Carvalho Gisah A de Carvalho Luciana A Castroneves Francisco M de Castro Jr Lucieli Ceolin Janete M Cerutti Rossana Corbo Tânia M B L Ferraz Carla V Ferreira M Inez C França Henrique C R Galvão Fausto Germano-Neto Hans Graf Alexander A L Jorge Ilda S Kunii Márcio W Lauria Vera L G Leal Susan C Lindsey Delmar M Lourenço Jr Léa M Z Maciel Patrícia K R Magalhães João R M Martins M Cecília Martins-Costa Gláucia M F S Mazeto Anelise I Impellizzeri Célia R Nogueira Edenir I Palmero Cencita H C N Pessoa Bibiana Prada Débora R Siqueira Maria Sharmila A Sousa Rodrigo A Toledo Flávia O F Valente Fernanda Vaisman Laura S Ward Shana S Weber Rita V Weiss Ji H Yang Magnus R Dias-da-Silva Ana O Hoff Sergio P A Toledo Ana L Maia Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study Endocrine Connections RET Brazil multiple endocrine neoplasia medullary thyroid carcinoma pheochromocytoma |
| title | Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study |
| title_full | Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study |
| title_fullStr | Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study |
| title_full_unstemmed | Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study |
| title_short | Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study |
| title_sort | genotype and phenotype landscape of men2 in 554 medullary thyroid cancer patients the brasmen study |
| topic | RET Brazil multiple endocrine neoplasia medullary thyroid carcinoma pheochromocytoma |
| url | https://ec.bioscientifica.com/view/journals/ec/8/3/EC-18-0506.xml |
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