文章：

甲状腺髓样癌的分子基础与自然病程：RET基因几乎决定一切

Molecular Basis and Natural History of Medullary Thyroid Cancer: It is (Almost) All in theRET

原文发布日期：5 October 2023

DOI: 10.3390/cancers15194865

类型: Article

开放获取: 是

英文摘要：

Medullary thyroid cancer (MTC) is a rare disease, which can be either sporadic (roughly 75% of cases) or genetically determined (multiple endocrine neoplasia type 2, due to REarranged during TransfectionRETgermline mutations, 25% of cases). Interestingly,RETpathogenic variants (mainly M918T) have also been reported in aggressive forms of sporadic MTC, suggesting the importance ofRETsignalling pathways in the pathogenesis of MTC. The initial theory ofRETcodon-related MTC aggressiveness has been recently questioned by studies suggesting that this would only define the age at disease onset rather than the aggressiveness of MTC. Other factors might however impact the natural history of the disease, such asRETpolymorphisms, epigenetic factors, environmental factors,MET(mesenchymal–epithelial transition) alterations, or even other genetic alterations such asRASfamily (HRAS,KRAS,NRAS) genetic alterations. This review will detail the molecular bases of MTC, focusing onRETpathways, and the potential mechanisms that explain the phenotypic intra- and interfamilial heterogeneity.

摘要翻译： 

甲状腺髓样癌（MTC）是一种罕见疾病，可分为散发性（约占病例的75%）和遗传性（多发性内分泌腺瘤病2型，由转染重排RET基因种系突变引起，占25%）。值得注意的是，侵袭性散发性MTC中也报道了RET致病性变异（主要为M918T），这提示RET信号通路在MTC发病机制中的重要性。近期研究对RET密码子与MTC侵袭性相关的初始理论提出质疑，认为其仅能界定疾病发病年龄而非侵袭性程度。然而其他因素可能影响疾病的自然病程，例如RET多态性、表观遗传因素、环境因素、MET（间质-上皮转化）改变，甚至包括RAS家族（HRAS、KRAS、NRAS）基因改变等其他遗传变异。本综述将详细阐述MTC的分子基础，重点关注RET通路，并探讨解释家族内及家族间表型异质性的潜在机制。

原文链接：

Molecular Basis and Natural History of Medullary Thyroid Cancer: It is (Almost) All in theRET