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

Santos, Marcos Ferreira; Quedas, Elisangela P S; Toledo, Rodrigo de Almeida; Lourenço-Júnior, Delmar M.; Toledo, Sergio Pereira de Almeida

doi:10.1590/s0004-27302007000900009

Cited by 8 publications

(4 citation statements)

References 31 publications

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“…In the post-genomic phase, we have used automated sequencing mutation analysis of the RET protooncogene 47,48. In the RET study, we have shown the efficiency of screening methods such as SSCP, DGGE and CSGE 28,47,48,52. Abelin et al34 conducted the first measurements of calcitonin in a limited set of patients presenting with a single, solid thyroid nodule and advocate calcitonin measurement as a routine procedure.…”

Section: Introductionmentioning

confidence: 99%

Hypercalcitoninemia is not Pathognomonic of Medullary Thyroid Carcinoma

Toledo

Lourenço

Santos

et al. 2009

Clinics

124

118

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Hypercalcitoninemia has frequently been reported as a marker for medullary thyroid carcinoma. Currently, calcitonin measurements are mostly useful in the evaluation of tumor size and progression, and as an index of biochemical improvement of medullary thyroid carcinomas. Although measurement of calcitonin is a highly sensitive method for the detection of medullary thyroid carcinoma, it presents a low specificity for this tumor. Several physiologic and pathologic conditions other than medullary thyroid carcinoma have been associated with increased levels of calcitonin. Several cases of thyroid nodules associated with increased values of calcitonin are not medullary thyroid carcinomas, but rather are related to other conditions, such as hypercalcemias, hypergastrinemias, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, and goiter. Furthermore, prolonged treatment with omeprazole (> 2–4 months), beta-blockers, glucocorticoids and potential secretagogues, have been associated with hypercalcitoninemia. An association between calcitonin levels and chronic auto-immune thyroiditis remains controversial. Patients with calcitonin levels >100 pg/mL have a high risk for medullary thyroid carcinoma (~90%–100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, < 5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary thyroid carcinoma.In multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventive thyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive calcitonin results within MEN2 families have led to incorrect indications of preventive total thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis of medullary thyroid carcinoma and consequent incorrect recommendation for thyroid surgery.

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Section: Introductionmentioning

confidence: 99%

Hypercalcitoninemia is not Pathognomonic of Medullary Thyroid Carcinoma

Toledo

Lourenço

Santos

et al. 2009

Clinics

124

118

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“…A routine search for RET germline mutations in all cases that presented with MTC and/or pheochromocytoma and in at-risk family members from MEN2 genealogies is recommended worldwide and is frequently performed in Brazil. 30 – 32 This procedure has been critical in the early detection of RET mutation carriers and has prompted the recommendation of prophylactic total thyroidectomy in the case of younger RET -positive carriers. 10 This may dramatically modify the outcome of MTC in MEN2 and may lead to a definitive surgical and biochemical cure of this disease in younger, asymptomatic RET -positive carriers.…”

Section: Discussionmentioning

confidence: 99%

“…DNA extraction : Peripheral blood was collected from all patients and screened for RET mutations as previously reported. 29 – 32 All patients signed an informed consent form before their blood was collected.…”

Section: Methodsmentioning

confidence: 99%

Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

Correia-Deur

Toledo

Imazawa

et al. 2009

Clinics

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INTRODUCTION:Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75%) or in a multiple endocrine neoplasia type 2 form (MEN2, 25%). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored. PURPOSE: To document the phenotypes observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended. METHOD: Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations. RESULTS:The average age at diagnosis was 43.9 years (± 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54%) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6% of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6-15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7%) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8%). Immunocyto-and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene. CONCLUSION: Our cases were identified late. The basal calcitonin measurements and immunostaining for calcitonin were highly useful for diagnosing s-medullary thyroid carcinoma. The rate of complete patient recovery was low, and none of the parameters analyzed were useful predictors of the thyroid tumor size. Our findings support previous recommendations for routine serum calcitonin evaluation and immunostaining analysis involving single thyroid nodules.

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“…O CSGE é um método utilizado par avaliar a variação de sequências em genes com vários éxons e parece apresentar maior sensibilidade do que outros métodos como SSCP, DGGE e enzimas de restrição. Um estudo de Santos e colaboradores (2007) Santos et al, 2007;Galeano et al, 2009;Ganguly, 2002).…”

Section: Diagnóstico Molecularunclassified

Estudo Do Polimorfismo E Diagnóstico Molecular Do Gene Causador Da Neoplasia Endócrina Múltipla Tipo 2b

Monteiro¹,

Costa²,

Queiroz³

2018

PIC

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A neoplasia endócrina múltipla tipo 2B é uma desordem de caráter autossômicodominante e é também a variante mais agressiva de todas as neoplasias endócrinasmúltiplas. Ela é causada por mutações de linhagem germinativa que induzem ganhode função do proto-oncogeneRET, responsável por codificar uma proteína do tipotirosina quinase que proporciona o controle da proliferação, diferenciação, migração eapoptose celular de células derivadas da crista neural. Aproximadamente metade doscasos são causados por mutações de novo no gene, portanto não possuem históricofamiliar. Entretanto, o rastreio genético para esta doença em grupos de risco consistena busca por mutações no proto-oncogeneRET durante os primeiros anos de vida. Oobjetivo desta pesquisa foi determinar o polimorfismo e a frequência do gene causadorda neoplasia endócrina múltipla tipo 2B em um grupo de indivíduos fumantes pormétodo molecular e definir padrões de influência genética e ambiental noaparecimento de mutações no gene RET.Primeiramente houve a produção de umartigo de revisão listando os mecanismos moleculares do gene de interesse e osprincipais métodos de rastreio e diagnóstico bioquímico e genético. A segunda partedo estudo realizado contou com a participação de vinte voluntários fumantes queestavam de acordo com o Termo de Consentimento Livre e Esclarecido proposto peloComitê de Ética. Foi encontrado um perfil de normalidade nas análises bioquímicas ehematológicas dos indivíduos e o questionário de controle de qualidade de vidarevelou que os voluntários se expõem com frequência à radiação solar e não mantêmum estilo de vida saudável, fatores que predispõem o aparecimento de mutações nogenoma. A análise por PCR-RFLP seguida de eletroforese em gel de agarose domaterial genético dos participantes não revelou a presençada mutação causadora daneoplasia endócrina múltipla tipo 2B

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

Cited by 8 publications

References 31 publications

Hypercalcitoninemia is not Pathognomonic of Medullary Thyroid Carcinoma

Hypercalcitoninemia is not Pathognomonic of Medullary Thyroid Carcinoma

Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

Estudo Do Polimorfismo E Diagnóstico Molecular Do Gene Causador Da Neoplasia Endócrina Múltipla Tipo 2b

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