M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds

Martins-Costa, Maria Cecilia [UNIFESP]; Cunha, Lucas Leite [UNIFESP]; Lindsey, Susan Chow [UNIFESP]; Camacho, Cléber Pinto [UNIFESP]; Dotto, Renata Pires [UNIFESP]; Furuzawa, Gilberto Koiti [UNIFESP]; Sousa, Maria Sharmila Alina de [UNIFESP]; Kasamatsu, Teresa Sayoko [UNIFESP]; Kunii, Ilda Sizue [UNIFESP]; Martins, Marcio Maciel [UNIFESP]; Machado, Alberto L. [UNIFESP]; Martins, João Roberto Maciel [UNIFESP]; Dias-da-Silva, Magnus Régios [UNIFESP]; Maciel, Rui Monteiro de Barros [UNIFESP]

M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds

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 M918...

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Autores:	Martins-Costa, Maria Cecilia [UNIFESP], Cunha, Lucas Leite [UNIFESP], Lindsey, Susan Chow [UNIFESP], Camacho, Cléber Pinto [UNIFESP], Dotto, Renata Pires [UNIFESP], Furuzawa, Gilberto Koiti [UNIFESP], Sousa, Maria Sharmila Alina de [UNIFESP], Kasamatsu, Teresa Sayoko [UNIFESP], Kunii, Ilda Sizue [UNIFESP], Martins, Marcio Maciel [UNIFESP], Machado, Alberto L. [UNIFESP], Martins, João Roberto Maciel [UNIFESP], Dias-da-Silva, Magnus Régios [UNIFESP], Maciel, Rui Monteiro de Barros [UNIFESP]
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2016
País:	Brasil
Institución:	Universidade Federal de São Paulo (UNIFESP)
Repositorio:	Repositório Institucional da UNIFESP
Idioma:	inglés
OAI Identifier:	oai:repositorio.unifesp.br:11600/56652
Acceso en línea:	http://dx.doi.org/10.1530/ERC-16-0141 https://repositorio.unifesp.br/handle/11600/56652
Access Level:	acceso abierto
Palabra clave:	medullary thyroid carcinoma RET mutation RET M918V founder effect

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spelling	M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindredsmedullary thyroidcarcinomaRET mutationRET M918Vfounder effectGermline 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 hyperplasiathe 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 2/20in 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.Univ Fed Sao Paulo, Escola Paulista Med, Thyroid Dis Ctr, Dept Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Div Endocrinol, Lab Mol & Translat Endocrinol, Sao Paulo, SP, BrazilHosp Geral Fortaleza, Ctr Endocrinol & Metabol, Fortaleza, Ceara, BrazilUniv Fortaleza, Dept Med, Fortaleza, Ceara, BrazilFleury Med & Hlth, Sao Paulo, SP, BrazilDepartment of Medicine, Thyroid Diseases Center, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, BrazilLaboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fleury Group Research GrantFAPESP: 2006/60402-1FAPESP: 2010/51547-1FAPESP: 2014/06570-6FAPESP: 2009/50575-4FAPESP: 2010/51546-5FAPESP: 2012/21942-1Fleury Group Research Grant: 12518Bioscientifica Ltd2020-07-31T12:47:12Z2020-07-31T12:47:12Z2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion909-920http://dx.doi.org/10.1530/ERC-16-0141Endocrine-Related Cancer. Bristol, v. 23, n. 12, p. 909-920, 2016.10.1530/ERC-16-01411351-0088https://repositorio.unifesp.br/handle/11600/56652WOS:000388940100015ark:/48912/001300002tgjvengEndocrine-Related CancerBristolinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPMartins-Costa, Maria Cecilia [UNIFESP]Cunha, Lucas Leite [UNIFESP]Lindsey, Susan Chow [UNIFESP]Camacho, Cléber Pinto [UNIFESP]Dotto, Renata Pires [UNIFESP]Furuzawa, Gilberto Koiti [UNIFESP]Sousa, Maria Sharmila Alina de [UNIFESP]Kasamatsu, Teresa Sayoko [UNIFESP]Kunii, Ilda Sizue [UNIFESP]Martins, Marcio Maciel [UNIFESP]Machado, Alberto L. [UNIFESP]Martins, João Roberto Maciel [UNIFESP]Dias-da-Silva, Magnus Régios [UNIFESP]Maciel, Rui Monteiro de Barros [UNIFESP]2022-02-08T12:05:23Zoai:repositorio.unifesp.br:11600/56652Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652022-02-08T12:05:23Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
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 Cecilia [UNIFESP] medullary thyroid carcinoma RET mutation RET M918V founder effect
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
dc.creator.none.fl_str_mv	Martins-Costa, Maria Cecilia [UNIFESP] Cunha, Lucas Leite [UNIFESP] Lindsey, Susan Chow [UNIFESP] Camacho, Cléber Pinto [UNIFESP] Dotto, Renata Pires [UNIFESP] Furuzawa, Gilberto Koiti [UNIFESP] Sousa, Maria Sharmila Alina de [UNIFESP] Kasamatsu, Teresa Sayoko [UNIFESP] Kunii, Ilda Sizue [UNIFESP] Martins, Marcio Maciel [UNIFESP] Machado, Alberto L. [UNIFESP] Martins, João Roberto Maciel [UNIFESP] Dias-da-Silva, Magnus Régios [UNIFESP] Maciel, Rui Monteiro de Barros [UNIFESP]
author	Martins-Costa, Maria Cecilia [UNIFESP]
author_facet	Martins-Costa, Maria Cecilia [UNIFESP] Cunha, Lucas Leite [UNIFESP] Lindsey, Susan Chow [UNIFESP] Camacho, Cléber Pinto [UNIFESP] Dotto, Renata Pires [UNIFESP] Furuzawa, Gilberto Koiti [UNIFESP] Sousa, Maria Sharmila Alina de [UNIFESP] Kasamatsu, Teresa Sayoko [UNIFESP] Kunii, Ilda Sizue [UNIFESP] Martins, Marcio Maciel [UNIFESP] Machado, Alberto L. [UNIFESP] Martins, João Roberto Maciel [UNIFESP] Dias-da-Silva, Magnus Régios [UNIFESP] Maciel, Rui Monteiro de Barros [UNIFESP]
author_role	author
author2	Cunha, Lucas Leite [UNIFESP] Lindsey, Susan Chow [UNIFESP] Camacho, Cléber Pinto [UNIFESP] Dotto, Renata Pires [UNIFESP] Furuzawa, Gilberto Koiti [UNIFESP] Sousa, Maria Sharmila Alina de [UNIFESP] Kasamatsu, Teresa Sayoko [UNIFESP] Kunii, Ilda Sizue [UNIFESP] Martins, Marcio Maciel [UNIFESP] Machado, Alberto L. [UNIFESP] Martins, João Roberto Maciel [UNIFESP] Dias-da-Silva, Magnus Régios [UNIFESP] Maciel, Rui Monteiro de Barros [UNIFESP]
author2_role	author author author author author author author author author author author author author
dc.subject.por.fl_str_mv	medullary thyroid carcinoma RET mutation RET M918V founder effect
topic	medullary thyroid carcinoma RET mutation RET M918V founder effect
description	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
publishDate	2016
dc.date.none.fl_str_mv	2016 2020-07-31T12:47:12Z 2020-07-31T12:47:12Z
dc.type.driver.fl_str_mv	info:eu-repo/semantics/article
dc.type.status.fl_str_mv	info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.uri.fl_str_mv	http://dx.doi.org/10.1530/ERC-16-0141 Endocrine-Related Cancer. Bristol, v. 23, n. 12, p. 909-920, 2016. 10.1530/ERC-16-0141 1351-0088 https://repositorio.unifesp.br/handle/11600/56652 WOS:000388940100015
dc.identifier.dark.fl_str_mv	ark:/48912/001300002tgjv
url	http://dx.doi.org/10.1530/ERC-16-0141 https://repositorio.unifesp.br/handle/11600/56652
identifier_str_mv	Endocrine-Related Cancer. Bristol, v. 23, n. 12, p. 909-920, 2016. 10.1530/ERC-16-0141 1351-0088 WOS:000388940100015 ark:/48912/001300002tgjv
dc.language.iso.fl_str_mv	eng
language	eng
dc.relation.none.fl_str_mv	Endocrine-Related Cancer
dc.rights.driver.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	909-920
dc.coverage.none.fl_str_mv	Bristol
dc.publisher.none.fl_str_mv	Bioscientifica Ltd
publisher.none.fl_str_mv	Bioscientifica Ltd
dc.source.none.fl_str_mv	reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP
instname_str	Universidade Federal de São Paulo (UNIFESP)
instacron_str	UNIFESP
institution	UNIFESP
reponame_str	Repositório Institucional da UNIFESP
collection	Repositório Institucional da UNIFESP
repository.name.fl_str_mv	Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv	biblioteca.csp@unifesp.br
_version_	1853670625637302272
score	15,301603

M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds

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