The role of genetic and epigenetic changes in pituitary tumorigenesis.
The role of genetic and epigenetic changes in pituitary tumorigenesis.
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DOI：
10.2176/nmc.ra.2014-0184
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发表时间：
2014
影响因子：
1.9
通讯作者：
Takahashi Y
中科院分区：
文献类型：
--
作者：
Fukuoka H;Takahashi Y
垂体腺瘤是最常见的颅内肿瘤之一。尽管它们是良性的，但激素分泌失调会引起全身代谢恶化，导致高死亡率和生活质量受损。垂体腺瘤的发生机制主要通过对肿瘤中的体细胞突变或患者的种系突变进行遗传分析来研究。基因改良的小鼠模型，发展垂体腺瘤，也被使用。对罕见的家族性垂体腺瘤，包括1型和4型多发性内分泌瘤、卡尼复合物、家族性孤立性垂体腺瘤和琥珀酸脱氢酶（SDHs）介导的副神经节瘤综合征的遗传分析显示，这些基因存在几种因果性种系突变和散发性体细胞突变。对垂体腺瘤的转基因小鼠模型的分析揭示了垂体瘤发生的潜在机制，其中细胞周期调节分子、肿瘤抑制因子和生长因子信号通路参与了垂体瘤的发生。此外，越来越多的证据表明，包括脱氧核糖核酸（DNA）甲基化、组蛋白修饰、微核糖核酸（rna）和长链非编码rna在内的表观遗传变化发挥了关键作用。阐明垂体腺瘤发生的确切机制有助于开发新的垂体腺瘤靶向治疗方法。
Pituitary adenomas are one of the most common intracranial tumors. Despite their benign nature, dys-regulation of hormone secretion causes systemic metabolic deterioration, resulting in high mortality and an impaired quality of life. Tumorigenic pathogenesis of pituitary adenomas is mainly investigated by performing genetic analyses of somatic mutations in the tumor or germline mutations in patients. Genetically modified mouse models, which develop pituitary adenomas, are also used. Genetic analysis in rare familial pituitary adenomas, including multiple endocrine neoplasia type 1 and type 4, Carney complex, familial isolated pituitary adenomas, and succinate dehydrogenases (SDHs)-mediated paraganglioma syndrome, revealed several causal germline mutations and sporadic somatic mutations in these genes. The analysis of genetically modified mouse models exhibiting pituitary adenomas has revealed the underlying mechanisms, where cell cycle regulatory molecules, tumor suppressors, and growth factor signaling are involved in pituitary tumorigenesis. Furthermore, accumulating evidence suggests that epigenetic changes, including deoxyribonucleic acid (DNA) methylation, histone modification, micro ribonucleic acids (RNAs), and long noncoding RNAs play a pivotal role. The elucidation of precise mechanisms of pituitary tumori-genesis can contribute to the development of novel targeted therapy for pituitary adenomas.