分化型甲状腺癌相关基因的研究进展

Recent advances in genes related to differentiated thyroid cancer

目的:总结近年来国内外分化型甲状腺癌(DTC)相关基因的研究进展。方法:应用PubMed、Elsevier Sciencedirect、CNKI及万方期刊全文数据库检索系统,以"分化型甲状腺癌、RET、Ras、BRAF"等为关键词,检索是2005-2010年发表的相关文献,共检索到文献252条。纳入标准:1)相关基因与分化型甲状腺癌发生、发展。2)相关基因与分化型甲状腺癌诊断、治疗及预后。根据纳入标准,纳入分析文献36篇。结果:甲状腺癌是最常见的内分泌肿瘤,近年来其发病率逐年增高,研究显示甲状腺癌的发生、发展是在不同的时间和空间上以多个原癌基因激活和(或)抑癌基因的失活为基础的多步骤过程。不同的病理类型有其相对特异性的基因改变:RET/PTC重排、BRAF突变多见于乳头状腺癌(papillary thyroid cancer,PTC),而Ras基因突变、PAX8-PPARG融合基因主要见于滤泡状腺癌(follicular thyroid cancer,FTC)。此外抑癌基因p53突变在甲状腺癌进展中起重要作用,PTEN则通过使PI3K/Akt的信号转导通路的持续激活促进了甲状腺癌的发生发展。相关的信号转导通路也参与其中。将有关基因用于分化型甲状腺癌的诊断、治疗、疗效预测及预后分析有着广阔的前景。结论:分化型甲状腺癌是个多因素多基因的疾病,其发生发展与基因的改变密切相关。

OBJECTIVE： To review the recent advances in genes related to differentiated thyroid cancer. METHODS： Using differentiated thyroid cancer, RET, Ras, BRAF etc as key words, the articles published from the databases such as Elsevier Sciencedirect, PubMed, Wanfang and CNKI, particularly from 2005 to 2010 were searched. Totally 252 articles were collected. Inclusion Criteria： 1） Association of related genes with develop- ment of differentiated thyroid cancer. 2） Association of related genes with diagnosis, treatment and prognosis of differentiated thyroid cancer. 36 articles were selected into analysis according to inclusion criteria. RESULTS= Thyroid cancer, 900/oo of which are differentiated thyroid cancer, is the most common endocrine ma- lignancy and catch people＇s attention for its increasing incidence in recent years. It is demonstrated that tumorigenesis of thyroid cancer is a multiple stage process, including activation of onco- genes and/or inactivation of tumor suppressor genes. Specific ge- netic lesions are associated to each thyroid tumor histotype： BRAF mutations and RET/PTC rearrangements have been detec ted in PTC, whereas FTC is characterized by PAX8-PPARG rear- rangements and ias mutations. Moreover, p53 mutations have a tumor progression role in thyroid tumorigenesis while aberrations of tumor suppressor PTEN enhance the signaling of PI3K/AKT pathway contribute to the progression of thyroid tumors. Related signaling pathways are also involved in the initiation and progres- sion of thyroid cancer. Using related genes to manage differentia- ted thyroid cancer will gain a wide prospect. CONCLUSION： Dif ferentiated thyroid cancer is a multigenic disease, its initiation and progression has close relation with genetic abnormality.