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

dc.creatorMartins-Costa, Maria Cecília
dc.creatorCunha, Lucas L.
dc.creatorLindsey, Susan C.
dc.creatorCamacho, Cleber P.
dc.creatorDotto, Renata P.
dc.creatorFuruzawa, Gilberto K.
dc.creatorSousa, Maria Sharmila Alina de
dc.creatorKasamatsu, Teresa S.
dc.creatorKunii, Ilda S.
dc.creatorMartins, Márcio M.
dc.creatorMachado, Alberto L.
dc.creatorMartins, João R. M.
dc.creatorSilva, Magnus R. Dias da
dc.creatorMaciel, Rui M. B.
dc.date2020-07-07T14:25:52Z
dc.date2020-07-07T14:25:52Z
dc.date2016
dc.date.accessioned2023-09-26T22:19:16Z
dc.date.available2023-09-26T22:19:16Z
dc.identifierMARTINS-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.identifier1351-0088
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/42138
dc.identifier10.1530/ERC-16-0141
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8877804
dc.descriptionM. 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.
dc.descriptionGermline 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.
dc.formatapplication/pdf
dc.languagepor
dc.publisherBioscientifica Ltd.
dc.rightsopen access
dc.subjectCarcinoma, Medullary
dc.subjectFounder Effect
dc.subjectGerm-Line Mutation
dc.subjectMethionine
dc.subjectMultiple Endocrine Neoplasia Type 2a
dc.subjectProto-Oncogene Proteins c-ret
dc.subjectThyroid Neoplasms
dc.subjectAmino Acid Substitution
dc.subjectMutation, Missense
dc.subjectPedigree
dc.subjectValine
dc.subjectMedullary thyroid carcinoma
dc.subjectRET mutation
dc.subjectRET M918V
dc.subjectFounder effect
dc.subjectCarcinoma Medular
dc.subjectEfeito Fundador
dc.subjectMutação em Linhagem Germinativa
dc.subjectNeoplasia Endócrina Múltipla Tipo 2a
dc.subjectNeoplasias da Glândula Tireoide
dc.subjectProteínas Proto-Oncogênicas c-ret
dc.titleM918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds
dc.typeArticle


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