文章：

甲状腺癌的分子发病机制

Molecular pathogenesis and mechanisms of thyroid cancer

原文发布日期：2013-02-22

DOI: 10.1038/nrc3431

类型: Review Article

开放获取: 否

要点：

1. Thyroid cancer is a common endocrine malignancy, and exciting progress has occurred in recent years in understanding its molecular pathogenesis.
2. Genetic and epigenetic alterations are the driving forces of thyroid cancer. Examples of these alterations include mutations in BRAF (BRAF^V600E), RAS, PIK3CA, PTEN, TP53, β-catenin (CTNNB1), anaplastic lymphoma kinase (ALK) and isocitrate dehydrogenase 1 (IDH1), translocations (RET–PTC and paired box 8 (PAX8)–peroxisome proliferator-activated receptor-γ (PPARG)) and aberrant gene methylation.
3. At the core of the molecular pathogenesis of thyroid cancer is the uncontrolled activity of various signalling pathways, including the MAPK, PI3K–AKT, nuclear factor-κB (NF-κB), RASSF1–mammalian STE20-like protein kinase 1 (MST1)–forkhead box O3 (FOXO3), WNT–β-catenin, hypoxia-inducible factor 1α (HIF1α) and thyroid-stimulating hormone (TSH)–TSH receptor (TSHR) pathways.
4. The progression of thyroid cancer is a process of accumulation of genetic and epigenetic alterations with corresponding progressive derangements of signalling pathways. These are accompanied by numerous secondary molecular alterations, both in the cell and in the tumour microenvironment, which, acting in cooperation, amplify and synergize their impacts on thyroid tumorigenesis.
5. Aberrant silencing of thyroid iodide-handling genes and consequent loss of radioiodine avidity of thyroid cancer promoted by BRAF-V600E is a unique molecular pathological process in thyroid cancer, which causes the failure of radioiodine treatment.
6. The recent molecular findings provide unprecedented opportunities for further research and clinical development of novel molecular-based treatment strategies for thyroid cancer.

要点翻译：

1. 甲状腺癌是一种常见的内分泌恶性肿瘤，近年来在其分子发病机制的认识方面取得了令人振奋的进展。
2. 遗传学与表观遗传学改变是甲状腺癌的驱动因素，包括BRAF（BRAFV600E）、RAS、PIK3CA、PTEN、TP53、β-连环蛋白（CTNNB1）、间变性淋巴瘤激酶（ALK）及异柠檬酸脱氢酶1（IDH1）基因突变，RET–PTC和配对盒8（PAX8）–过氧化物酶体增殖物激活受体-γ（PPARG）易位，以及异常基因甲基化现象。
3. 甲状腺癌分子发病机制的核心在于多种信号通路的失控性激活，包括MAPK、PI3K–AKT、核因子-κB（NF-κB）、RASSF1–哺乳动物STE20样蛋白激酶1（MST1）–叉头框蛋白O3（FOXO3）、WNT–β-连环蛋白、缺氧诱导因子1α（HIF1α）及促甲状腺激素（TSH）–TSH受体（TSHR）通路。
4. 甲状腺癌的演进是遗传与表观遗传学改变逐步累积、相应信号通路进行性紊乱的过程。这一过程伴随着细胞及肿瘤微环境中大量次级分子改变，这些改变通过协同作用放大并增强了对甲状腺肿瘤发生的影响。
5. BRAF-V600E突变促进甲状腺摄碘基因异常沉默及随之引发的甲状腺癌放射性碘亲和力丧失，是甲状腺癌中独特的分子病理过程，该过程直接导致放射性碘治疗失效。
6. 近期分子研究发现为甲状腺癌的深入研究及开发基于分子的新型治疗策略提供了前所未有的机遇。

英文摘要：

Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer.

摘要翻译： 

甲状腺癌是一种常见的内分泌恶性肿瘤。近年来，在理解其分子发病机制方面取得了令人振奋的进展，其中最具代表性的例子是阐明了几个主要信号通路及其相关分子异常所发挥的根本性作用。这些机制的核心在于这些通路中的遗传和表观遗传改变，如突变、基因拷贝数增加以及异常的基因甲基化。许多这类分子改变代表了甲状腺癌的新型诊断和预后分子标志物以及治疗靶点，为进一步研究以及开发针对该癌症的新型治疗策略的临床发展提供了前所未有的机遇。

原文链接：

Molecular pathogenesis and mechanisms of thyroid cancer