Tumorigênese Molecular Tiroideana: Implicações Para a Prática Médica

Maciel, Rui M. B.

doi:10.1590/s0004-27302002000400009

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…Dois adolescentes com NEM-2B apresentam a mutação Met918Thr do proto-oncogene RET, que é a mais freqüentemente encontrada nos pacientes portadores desta síndrome (22).…”

Section: Discussionunclassified

Câncer de tireóide na infância e adolescência: relato de 15 casos

Cardoso

Pianovski

Nesi-França

et al. 2004

Arq Bras Endocrinol Metab

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RESUMOTumores tireoideanos são raros na infância e adolescência. Foram revisados os prontuários de quinze pacientes (8 do sexo feminino) com idades entre 5,8 e 15,2 anos, atendidos na Unidade de Endocrinologia Pediátrica (UEP) do HC-UFPR entre fevereiro de 1988 e março de 2003. Nódulo cervical anterior foi a queixa inicial mais freqüente. Dez pacientes eram portadores de carcinoma papilífero (CP), quatro apresentavam carcinoma medular (CMT; dos quais, três com NEM-2B) e um, carcinoma folicular. Dois pacientes com NEM-2B apresentam mutação de novo (M e t 9 1 8 T h r) do proto-oncogene R E T. PAAF, efetuada em dez pacientes, foi positiva para neoplasia em cinco deles. Todos os pacientes foram submetidos a tireoidectomia total. Terapia adjuvante com 1 3 1 I foi realizada em dez pacientes. Dois pacientes faleceram por doença não relacionada ao tumor. Nove pacientes não apresentam evidência clínica ou laboratorial do tumor; um (CP) apresentou recidiva 5 anos após o tratamento inicial e três (1 CP, 2 CMT) ainda têm evidência da doença. Nossos dados estão de acordo com a literatura em relação ao prognóstico e manifestações clínicas. Entretanto, a prevalência de CMT (27%), a distribuição por sexo e os resultados da PAAF diferem da maioria das casuísticas publicadas, o que pode ser atribuído ao número de casos aqui relatado. The most frequent initial complaint was an anterior cervical nodule. Ten patients were papillary carcinoma (PTC) bearers, four had medullary carcinoma (MTC; three of them with MEN-2B) and one had follicular carcinoma. Two patients with MEN-2B have de novo proto-oncogene R E T mutation (M e t 9 1 8 T h r). Fine needle aspiration (FNA) was performed in ten patients and was malignancy positive in only five of them. All patients underwent total thyroidectomy. Adjuvant radioiodine ( 1 3 1 I) therapy was made in ten patients. Two patients died from unrelated diseases. Nine patients presented no clinical or laboratorial evidence of disease; one (PTC) developed recurrence 5 years after initial treatment and three (1 PTC, 2 MTC) have disease evidence yet. Our prognosis and clinical manifestations data are according to the literature. However, MTC prevalence (27%), sex distribution and FNA results differ from the majority of published casuistics, that can be atributed to the number of cases reported here.

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“…Dois adolescentes com NEM-2B apresentam a mutação Met918Thr do proto-oncogene RET, que é a mais freqüentemente encontrada nos pacientes portadores desta síndrome (22).…”

Section: Discussionunclassified

Câncer de tireóide na infância e adolescência: relato de 15 casos

Cardoso

Pianovski

Nesi-França

et al. 2004

Arq Bras Endocrinol Metab

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“…All individuals have been followed at the Outpatient Service of the Division of Endocrinology, Hospital das Clínicas, University of Sao Paulo School of Medicine. Index cases were diagnosed by classical clinical, biochemical, and genetic parameters (2,3,(8)(9)(10)(11)(12)15).…”

Section: Patientsmentioning

confidence: 99%

“…RET hot-spots exons (10,11,13,14,15, and 16) of all index cases (7 subjects) and in one genetically non- Val804Met mutation and Ser904Ser polymorphism were not included in this table.…”

Section: Sequencing Analysismentioning

confidence: 99%

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Screening of RET gene mutations in multiple endocrine neoplasia type-2 using Conformation Sensitive Gel Electrophoresis (CSGE)

Santos

Quedas

Toledo

et al. 2007

Arq Bras Endocrinol Metab

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Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited tumor syndrome caused by RET proto-oncogene germline mutations (RET). Here we tested the Conformation Sensitive Gel Electrophoresis (CSGE) as a screening method for RET hot-spot mutations. Seven MEN2 families were studied by direct sequencing analysis, CSGE and Single Strand Conformational Polymorphism (SSCP). Using CSGE/SSCP, we were able to detect four out of five types of RET mutations verified by sequencing analysis: Cys620Arg, Cys634Arg, Cys634Tyr, and Met918Thr, furthermore a missense substitution at codon 648 (Val648Ile). RET polymorphisms 691 and 769 were also verified. Data obtained using CSGE/SSCP were fully concordant. We conclude that CSGE showed to be a sensitive, fast, low-cost, and simple procedure to detect RET mutations in codons which are reported as the most prevalent RET variants (~ 95%) in large MEN2 series. As to the Val804Met mutation, this method still needs to be optimized. RESUMO Rastreamento de Mutações do Gene RET na Neoplasia Endócrina Múltipla Tipo 2 por Eletroforese em Gel Sensível à Conformação (CSGE).A neoplasia endócrina múltipla tipo 2 (NEM2) é uma síndrome tumoral herdada por mutações germinativas no proto-oncogene RET (RET). Analisamos a aplicação do método Eletroforese em Gel Sensível à Conformação (CSGE) no rastreamento de mutações hot spots do RET. Sete famílias com NEM2 foram rastreadas pelo seqüenciamento gênico, CSGE e análise do Polimorfismo Conformacional de Cadeia Simples (SSCP). Usando ambas as metodologias de rastreamento, identificamos quatro dos cinco tipos de mutações verificadas pelo seqüenciamento: Cys620Arg, Cys634Arg, Cys634Tyr e Met918Thr, além da variação gênica Val648Ile. Das análises englobando mutações hot spots do RET, 90,6% concordaram com o seqüenciamento genético (incluindo a variação gênica Val648Ile). Polimorfismos nos códons 691 e 769 foram documentados. Os dados obtidos por CSGE/SSCP foram totalmente concordantes. Concluímos que o CSGE revelou ser metodologia sensível, rápida, de fácil execução e baixo custo no rastreamento de mutações nos códons associados à grande maioria (~ 95%) dos pacientes com NEM2. (Arq Bras Endocrinol Metab

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“…[28][29][30][31][32] At the stage of palpable thyroid nodules, MTC measures at least 1 cm, and 50% of patients already have local neck lymph node metastases and more rarely lung, liver, and bone metastases. 33,34 It has been suggested that routine calcitonin measurements should be performed in all patients with solid thyroid nodules, since this procedure would permit presurgical diagnosis of the sporadic form of MTC as well 35,36 Fine-needle biopsy followed by immunocytochemistry for calcitonin is also helpful for the presurgical diagnosis of MTC. 1,11,12,[37][38][39][40] Total thyroidectomy associated with extensive resection of neck lymph nodes is the only effective treatment for MTC, as the tumor is usually resistant to iodo-, chemo-, and radiotherapy.…”

Section: Medullary Thyroid Carcinoma (Mtc)mentioning

confidence: 99%

Impact of Ret Proto-Oncogene Analysis on the Clinical Management of Multiple Endocrine Neoplasia Type 2

Toledo

Santos

Toledo

et al. 2006

Clinics

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Toledo SPA, Cortina MA, Toledo RA, Lourenço, DM. Impact of RET proto-oncogene analysis on the clinical management of multiple endocrine neoplasia type 2. Clinics. 2006:61(1);59-70.Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, primary hyperparathyroidism, and pheochromocytoma. Multiple endocrine neoplasia type 2 is still an underdiagnosed, or late-diagnosed condition in many areas of the world. Since 1993, when the first missense RET proto-oncogene (RET) mutations were reported in MEN2, up to 46 different RET-causing disease mutations have been described. Since a strong genotype-phenotype correlation exists for MEN2, the detection of RET mutations has produced a major impact in early recognition and treatment of MTC and MEN2. Presently, RET mutation analysis should be performed for all MEN2 cases and their at-risk familial relatives. Further, prophylactic total thyroidectomy is indicated in all cases harboring activating gametic RET mutations. In most RET mutation carriers, prophylactic total thyroidectomy is indicated at ages as early as a few months to 4 years of age, promoting longer survival and improvement of quality of life or even definitive cure. We discuss the large impact of RET protooncogene analysis on the clinical management of MEN2 and the role of early RET molecular DNA diagnosis in providing clinicians and surgeons with valuable information that enables them to indicate early total thyroidectomy.

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Tumorigênese Molecular Tiroideana: Implicações Para a Prática Médica

Cited by 8 publications

References 21 publications

Câncer de tireóide na infância e adolescência: relato de 15 casos

Câncer de tireóide na infância e adolescência: relato de 15 casos

Screening of RET gene mutations in multiple endocrine neoplasia type-2 using Conformation Sensitive Gel Electrophoresis (CSGE)

Impact of Ret Proto-Oncogene Analysis on the Clinical Management of Multiple Endocrine Neoplasia Type 2

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