M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds
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| Publication Date: | 2016 |
| Other Authors: | , , , , , , , , , , , , |
| Format: | Article |
| Language: | por |
| Source: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.1530/ERC-16-0141 |
| Download full: | https://arca.fiocruz.br/handle/icict/42138 |
Summary: | M. Sharmila A. Sousa - Fundação Oswaldo Cruz. Fiocruz Brasília. Brasília, DF, Brasil. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento. |
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Martins-Costa, Maria CecíliaCunha, Lucas L.Lindsey, Susan C.Camacho, Cleber P.Dotto, Renata P.Furuzawa, Gilberto K.Sousa, Maria Sharmila Alina deKasamatsu, Teresa S.Kunii, Ilda S.Martins, Márcio M.Machado, Alberto L.Martins, João R. M.Silva, Magnus R. Dias daMaciel, Rui M. B.2020-07-07T14:25:52Z2020-07-07T14:25:52Z2016MARTINS-COSTA, M. Cecília et al. M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds. Endocrine-Related Cancer, [s.l], v. 23, n.12, p. 909–920, 2016.1351-0088https://arca.fiocruz.br/handle/icict/4213810.1530/ERC-16-0141M. Sharmila A. Sousa - Fundação Oswaldo Cruz. Fiocruz Brasília. Brasília, DF, Brasil. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil / Hospital Geral de Fortaleza. Center for Endocrinology and Metabology. Fortaleza, CE, Brasil / Universidade de Fortaleza. Department of Medicine. Fortaleza, CE, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil / Fleury Medicine and Health. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Endocrinology. Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology. Department of Medicine. São Paulo, SP, Brasil / Fleury Medicine and Health. São Paulo, SP, Brasil.Germline mutations in codon 918 of exon 16 of the RET gene (M918T) are classically associated with multiple endocrine neoplasia type 2B (MEN 2B) with highly aggressive medullary thyroid cancer (MTC), pheochromocytoma and a unique phenotype. The objectives of this study are to describe the rare M918V RET mutation discovered in 8 MTC kindreds from Brazil lacking the MEN 2B phenotype classically observed in M918T patients and to investigate the presence of a founder effect for this germline mutation. Eight apparently sporadic MTC cases were diagnosed with the germline M918V RET mutation. Subsequently, their relatives underwent clinical and genetic assessment (n = 113), and M918V was found in 42 of them. Until today, 20/50 M918V carriers underwent thyroidectomy and all presented MTC/C-cell hyperplasia; the remainder carriers are on clinical follow-up. None of the M918V carriers presented clinical features of MEN 2B. Their clinical presentation was heterogeneous, and the age at tumor diagnosis ranged from 24 to 59 years. Lymph node metastases were present in 12/20 patients, and presumable distant metastases in 2/20; in contrast, we observed a carrier of up to 87 years of age without evidence of MTC. Ethnographic fieldwork and haplotype analyses suggested that the founder mutation first settled in that area fifteen generations ago and originated from Portugal. Our study is the first to demonstrate the RET M918V mutation co-segregating in 8 familial MTC kindreds with validated evidence of a founder effect. We suggest that M918V MTC should be clinically considered an American Thyroid Association (ATA) moderate-risk category.porBioscientifica Ltd.Carcinoma, MedullaryFounder EffectGerm-Line MutationMethionineMultiple Endocrine Neoplasia Type 2aProto-Oncogene Proteins c-retThyroid NeoplasmsAmino Acid SubstitutionMutation, MissensePedigreeValineMedullary thyroid carcinomaRET mutationRET M918VFounder effectCarcinoma MedularEfeito FundadorMutação em Linhagem GerminativaNeoplasia Endócrina Múltipla Tipo 2aNeoplasias da Glândula TireoideProteínas Proto-Oncogênicas c-retM918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindredsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83074https://arca.fiocruz.br/bitstreams/93501e06-bc3d-4419-b405-4fd654d5181a/downloadd3e717dbb24bfc607ede047f44d29a0eMD51falseAnonymousREADORIGINALve_Maria_Sousa_etal.pdfve_Maria_Sousa_etal.pdfapplication/pdf1265731https://arca.fiocruz.br/bitstreams/f1195997-aebc-4e40-a67a-1544193a8bdd/download87745b5fb4edf0a855ee1f4f8bf41fdcMD52trueAnonymousREADTEXTve_Maria_Sousa_etal.pdf.txtve_Maria_Sousa_etal.pdf.txtExtracted texttext/plain62423https://arca.fiocruz.br/bitstreams/3be407c8-5ba1-4898-85fa-72abfe99120b/downloadcbac299bff85bca371022e0f7074ddd5MD55falseAnonymousREADTHUMBNAILve_Maria_Sousa_etal.pdf.jpgve_Maria_Sousa_etal.pdf.jpgGenerated Thumbnailimage/jpeg6133https://arca.fiocruz.br/bitstreams/40c3830a-0eb8-4686-bd7a-0c452c563bba/downloadec76bc73cae21ece29a5e00d6946d488MD56falseAnonymousREADicict/421382025-07-29 23:21:38.75open.accessoai:arca.fiocruz.br:icict/42138https://arca.fiocruz.brRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352025-07-30T02:21:38Repositório Institucional da FIOCRUZ (ARCA) - 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| dc.title.none.fl_str_mv |
M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds |
| title |
M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds |
| spellingShingle |
M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds Martins-Costa, Maria Cecília Carcinoma, Medullary Founder Effect Germ-Line Mutation Methionine Multiple Endocrine Neoplasia Type 2a Proto-Oncogene Proteins c-ret Thyroid Neoplasms Amino Acid Substitution Mutation, Missense Pedigree Valine Medullary thyroid carcinoma RET mutation RET M918V Founder effect Carcinoma Medular Efeito Fundador Mutação em Linhagem Germinativa Neoplasia Endócrina Múltipla Tipo 2a Neoplasias da Glândula Tireoide Proteínas Proto-Oncogênicas c-ret |
| title_short |
M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds |
| title_full |
M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds |
| title_fullStr |
M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds |
| title_full_unstemmed |
M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds |
| title_sort |
M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds |
| author |
Martins-Costa, Maria Cecília |
| author_facet |
Martins-Costa, Maria Cecília Cunha, Lucas L. Lindsey, Susan C. Camacho, Cleber P. Dotto, Renata P. Furuzawa, Gilberto K. Sousa, Maria Sharmila Alina de Kasamatsu, Teresa S. Kunii, Ilda S. Martins, Márcio M. Machado, Alberto L. Martins, João R. M. Silva, Magnus R. Dias da Maciel, Rui M. B. |
| author_role |
author |
| author2 |
Cunha, Lucas L. Lindsey, Susan C. Camacho, Cleber P. Dotto, Renata P. Furuzawa, Gilberto K. Sousa, Maria Sharmila Alina de Kasamatsu, Teresa S. Kunii, Ilda S. Martins, Márcio M. Machado, Alberto L. Martins, João R. M. Silva, Magnus R. Dias da Maciel, Rui M. B. |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Martins-Costa, Maria Cecília Cunha, Lucas L. Lindsey, Susan C. Camacho, Cleber P. Dotto, Renata P. Furuzawa, Gilberto K. Sousa, Maria Sharmila Alina de Kasamatsu, Teresa S. Kunii, Ilda S. Martins, Márcio M. Machado, Alberto L. Martins, João R. M. Silva, Magnus R. Dias da Maciel, Rui M. B. |
| dc.subject.mesh.none.fl_str_mv |
Carcinoma, Medullary Founder Effect Germ-Line Mutation Methionine Multiple Endocrine Neoplasia Type 2a Proto-Oncogene Proteins c-ret Thyroid Neoplasms Amino Acid Substitution Mutation, Missense Pedigree Valine |
| topic |
Carcinoma, Medullary Founder Effect Germ-Line Mutation Methionine Multiple Endocrine Neoplasia Type 2a Proto-Oncogene Proteins c-ret Thyroid Neoplasms Amino Acid Substitution Mutation, Missense Pedigree Valine Medullary thyroid carcinoma RET mutation RET M918V Founder effect Carcinoma Medular Efeito Fundador Mutação em Linhagem Germinativa Neoplasia Endócrina Múltipla Tipo 2a Neoplasias da Glândula Tireoide Proteínas Proto-Oncogênicas c-ret |
| dc.subject.en.none.fl_str_mv |
Medullary thyroid carcinoma RET mutation RET M918V Founder effect |
| dc.subject.decs.none.fl_str_mv |
Carcinoma Medular Efeito Fundador Mutação em Linhagem Germinativa Neoplasia Endócrina Múltipla Tipo 2a Neoplasias da Glândula Tireoide Proteínas Proto-Oncogênicas c-ret |
| description |
M. Sharmila A. Sousa - Fundação Oswaldo Cruz. Fiocruz Brasília. Brasília, DF, Brasil. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento. |
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2016 |
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2016 |
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2020-07-07T14:25:52Z |
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2020-07-07T14:25:52Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.citation.fl_str_mv |
MARTINS-COSTA, M. Cecília et al. M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds. Endocrine-Related Cancer, [s.l], v. 23, n.12, p. 909–920, 2016. |
| dc.identifier.uri.fl_str_mv |
https://arca.fiocruz.br/handle/icict/42138 |
| dc.identifier.issn.none.fl_str_mv |
1351-0088 |
| dc.identifier.doi.none.fl_str_mv |
10.1530/ERC-16-0141 |
| identifier_str_mv |
MARTINS-COSTA, M. Cecília et al. M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds. Endocrine-Related Cancer, [s.l], v. 23, n.12, p. 909–920, 2016. 1351-0088 10.1530/ERC-16-0141 |
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https://arca.fiocruz.br/handle/icict/42138 |
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por |
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por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Bioscientifica Ltd. |
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Bioscientifica Ltd. |
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