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

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dc.citation.issue12
dc.citation.volume23
dc.contributor.authorMartins-Costa, Maria Cecilia [UNIFESP]
dc.contributor.authorCunha, Lucas Leite [UNIFESP]
dc.contributor.authorLindsey, Susan Chow [UNIFESP]
dc.contributor.authorCamacho, Cléber Pinto [UNIFESP]
dc.contributor.authorDotto, Renata Pires [UNIFESP]
dc.contributor.authorFuruzawa, Gilberto Koiti [UNIFESP]
dc.contributor.authorSousa, Maria Sharmila Alina de [UNIFESP]
dc.contributor.authorKasamatsu, Teresa Sayoko [UNIFESP]
dc.contributor.authorKunii, Ilda Sizue [UNIFESP]
dc.contributor.authorMartins, Marcio Maciel [UNIFESP]
dc.contributor.authorMachado, Alberto L. [UNIFESP]
dc.contributor.authorMartins, João Roberto Maciel [UNIFESP]
dc.contributor.authorDias-da-Silva, Magnus Régios [UNIFESP]
dc.contributor.authorMaciel, Rui Monteiro de Barros [UNIFESP]
dc.coverageBristol
dc.date.accessioned2020-07-31T12:47:12Z
dc.date.available2020-07-31T12:47:12Z
dc.date.issued2016
dc.description.abstractGermline 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 hyperplasiaen
dc.description.abstractthe 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 2/20en
dc.description.abstractin 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.en
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Thyroid Dis Ctr, Dept Med, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Div Endocrinol, Lab Mol & Translat Endocrinol, Sao Paulo, SP, Brazil
dc.description.affiliationHosp Geral Fortaleza, Ctr Endocrinol & Metabol, Fortaleza, Ceara, Brazil
dc.description.affiliationUniv Fortaleza, Dept Med, Fortaleza, Ceara, Brazil
dc.description.affiliationFleury Med & Hlth, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespDepartment of Medicine, Thyroid Diseases Center, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil
dc.description.affiliationUnifespLaboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipFleury Group Research Grant
dc.description.sponsorshipIDFAPESP: 2006/60402-1
dc.description.sponsorshipIDFAPESP: 2010/51547-1
dc.description.sponsorshipIDFAPESP: 2014/06570-6
dc.description.sponsorshipIDFAPESP: 2009/50575-4
dc.description.sponsorshipIDFAPESP: 2010/51546-5
dc.description.sponsorshipIDFAPESP: 2012/21942-1
dc.description.sponsorshipIDFleury Group Research Grant: 12518
dc.format.extent909-920
dc.identifierhttp://dx.doi.org/10.1530/ERC-16-0141
dc.identifier.citationEndocrine-Related Cancer. Bristol, v. 23, n. 12, p. 909-920, 2016.
dc.identifier.doi10.1530/ERC-16-0141
dc.identifier.issn1351-0088
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56652
dc.identifier.wosWOS:000388940100015
dc.language.isoeng
dc.publisherBioscientifica Ltd
dc.relation.ispartofEndocrine-Related Cancer
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectmedullary thyroiden
dc.subjectcarcinomaen
dc.subjectRET mutationen
dc.subjectRET M918Ven
dc.subjectfounder effecten
dc.titleM918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindredsen
dc.typeinfo:eu-repo/semantics/article
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