Division of Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Cell Mol Life Sci. 2012 Jun;69(11):1799-811. doi: 10.1007/s00018-011-0898-9. Epub 2011 Dec 13.
Pilocytic astrocytoma (PA) is the most common tumor of the pediatric central nervous system (CNS). A body of research over recent years has demonstrated a key role for mitogen-activated protein kinase (MAPK) pathway signaling in the development and behavior of PAs. Several mechanisms lead to activation of this pathway in PA, mostly in a mutually exclusive manner, with constitutive BRAF kinase activation subsequent to gene fusion being the most frequent. The high specificity of this fusion to PA when compared with other CNS tumors has diagnostic utility. In addition, the frequency of alteration of this key pathway provides an opportunity for molecularly targeted therapy in this tumor. Here, we review the current knowledge on mechanisms of MAPK activation in PA and some of the downstream consequences of this activation, which are now starting to be elucidated both in vitro and in vivo, as well as clinical considerations and possible future directions.
毛细胞星形细胞瘤（PA）是儿童中枢神经系统（CNS）最常见的肿瘤。近年来的大量研究表明，丝裂原活化蛋白激酶（MAPK）途径信号在 PA 的发生和行为中起着关键作用。几种机制导致该途径在 PA 中被激活，主要以相互排斥的方式，最常见的是基因融合后组成性 BRAF 激酶激活。与其他 CNS 肿瘤相比，这种融合对 PA 的高特异性具有诊断意义。此外，这种关键途径改变的频率为该肿瘤的分子靶向治疗提供了机会。在这里，我们回顾了目前关于 PA 中 MAPK 激活机制及其下游后果的知识，这些知识现在开始在体外和体内得到阐明，以及临床考虑因素和可能的未来方向。
