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脑膜瘤的遗传/分子改变及靶向的信号通路

Genetic/molecular alterations of meningiomas and the signaling pathways targeted.

作者信息

Domingues Patrícia, González-Tablas María, Otero Álvaro, Pascual Daniel, Ruiz Laura, Miranda David, Sousa Pablo, Gonçalves Jesús María, Lopes María Celeste, Orfao Alberto, Tabernero María Dolores

机构信息

Centre for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.

Centre for Cancer Research (CIC-IBMCC, CSIC/USAL, IBSAL) and Department of Medicine, University of Salamanca, Salamanca, Spain.

出版信息

Oncotarget. 2015 May 10;6(13):10671-88. doi: 10.18632/oncotarget.3870.

Abstract

Meningiomas are usually considered to be benign central nervous system tumors; however, they show heterogenous clinical, histolopathological and cytogenetic features associated with a variable outcome. In recent years important advances have been achieved in the identification of the genetic/molecular alterations of meningiomas and the signaling pathways involved. Thus, monosomy 22, which is often associated with mutations of the NF2 gene, has emerged as the most frequent alteration of meningiomas; in addition, several other genes (e.g., AKT1, KLF4, TRAF7, SMO) and chromosomes have been found to be recurrently altered often in association with more complex karyotypes and involvement of multiple signaling pathways. Here we review the current knowledge about the most relevant genes involved and the signaling pathways targeted by such alterations. In addition, we summarize those proposals that have been made so far for classification and prognostic stratification of meningiomas based on their genetic/genomic features.

摘要

脑膜瘤通常被认为是良性中枢神经系统肿瘤;然而,它们表现出异质性的临床、组织病理学和细胞遗传学特征,其预后各不相同。近年来,在脑膜瘤的基因/分子改变及相关信号通路的识别方面取得了重要进展。因此,常与NF2基因突变相关的22号染色体单体缺失已成为脑膜瘤最常见的改变;此外,还发现其他几个基因(如AKT1、KLF4、TRAF7、SMO)和染色体经常发生改变,且往往与更复杂的核型以及多个信号通路的参与有关。在此,我们综述了有关最相关基因及此类改变所靶向的信号通路的当前知识。此外,我们总结了迄今为止基于脑膜瘤的基因/基因组特征进行分类和预后分层的提议。

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