Genetics of medullary thyroid cancer: An overview
| Autor: | Vittorio Colantuoni, Claudio Gambardella, Filomena Castaldo, Dario Giugliano, Daniela Esposito, Andrea Polistena, Giovanni Conzo, Carlo Di Donna, Daniela Pasquali, Nicola Avenia, Marco Mazzella, Giacomo Accardo |
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| Přispěvatelé: | Accardo, Giacomo, Conzo, Giovanni, Esposito, Daniela, Gambardella, Claudio, Mazzella, Marco, Castaldo, Filomena, Di Donna, Carlo, Polistena, Andrea, Avenia, Nicola, Colantuoni, Vittorio, Giugliano, Dario, Pasquali, Daniela |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
Pathology Medullary/genetics endocrine system diseases Pyridines medicine.medical_treatment Multiple Endocrine Neoplasia Type 2a Vandetanib Thyroid Neoplasms/surgery Proto-Oncogene Mas chemistry.chemical_compound Multiple Endocrine Neoplasia Type 2a/drug therapy 0302 clinical medicine Piperidines Exons/genetics Medullary/drug therapy Anilides Multiple endocrine neoplasia Pyridines/therapeutic use Anilides/therapeutic use Thyroid Medullary thyroid cancer General Medicine Exons Middle Aged medicine.anatomical_structure 030220 oncology & carcinogenesis Carcinoma Medullary Thyroidectomy Thyroid Neoplasms/genetics medicine.drug medicine.medical_specialty Genetic Proto-Oncogene Proteins c-ret/genetics Cabozantinib Quinazolines/therapeutic use 030209 endocrinology & metabolism Medullary/surgery Thyroid carcinoma 03 medical and health sciences medicine Carcinoma Carcinoma Medullary/congenital Carcinoma Medullary/drug therapy Carcinoma Medullary/genetics Carcinoma Medullary/surgery Codon/genetics Multiple Endocrine Neoplasia Type 2a/complications Multiple Endocrine Neoplasia Type 2a/genetics Multiple Endocrine Neoplasia Type 2a/surgery Mutation Piperidines/therapeutic use Polymorphism Genetic Proto-Oncogene Proteins c-ret/genetics Thyroid Neoplasms/drug therapy Humans Thyroid Neoplasms Polymorphism Codon Polymorphism Genetic business.industry Proto-Oncogene Proteins c-ret medicine.disease chemistry Mutation Cancer research Quinazolines Surgery business Medullary/congenital |
| Popis: | Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such asMEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved. In MEN2A, Codon 634 in exon 11 (Cys634Arg), corresponding to a cysteine in the extracellular cysteine-rich domain, is the most commonly altered codon. Many other mutations include codons 611, 618, 620. In the genetical testing of RET mutations in MTCs, Next-Generation Sequencing (NGS) is taking an increasingly important role. One of the most important benefit is the comprehensive analysis of molecular alterations in MTC, which allows rapidly to select patients with different risk levels. There is a difference in miRNA expression pathway between sporadic and hereditary MTCs. Among sporadic cases, expression of miR-127 was significantly lower in those who harbor somatic RET mutations than those with wild-type RET. CDKN1B mutations are associated with many clinical pictures of cancers, such as MEN4. V109G polymorphism is associated with sporadic MTCs negative for RET mutations, and might influence the clinical course of the patients affected by MTC. Although surgery (i.e. total thyroidectomy with neck lymph node dissection) is the elective treatment for MTCs, about 80% of patients have distant metastases at diagnosis and in this cases surgery is not enough and an additional treatment is needed. Interesting results come from two large phase III clinical trials with two targeted tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib. Conclusions: New genetical testings and therapeutical approaches open new perspectives in MTC management. (C) 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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