Genetic/molecular alterations of meningiomas and the signaling pathways targeted

// Patrícia Domingues 1,2 , María González-Tablas 2 , Álvaro Otero 3 , Daniel Pascual 3 , Laura Ruiz 3 , David Miranda 3 , Pablo Sousa 3 , Jesús María Gonçalves 3 , María Celeste Lopes 1 , Alberto Orfao 2 and María Dolores Tabernero 2,3 1 Centre for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal 2 Centre for Cancer Research (CIC-IBMCC, CSIC/USAL, IBSAL) and Department of Medicine, University of Salamanca, Salamanca, Spain 3 Neurosurgery Service, University Hospital of Salamanca, Salamanca, Spain 4 Instituto de Estudios de Ciencias de la salud de Castilla y León (IECSCYL-IBSAL) and Research Unit of the University Hospital of Salamanca, Salamanca, Spain Correspondence to: María Dolores Tabernero, email: // Keywords : genetic/molecular alteration; signal pathways; meningioma; chromosome 22 Received : March 09, 2015 Accepted : April 04, 2015 Published : April 19, 2015 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.