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.
Highlights
Meningiomas are one of the most frequent primary brain neoplasias –30-35% of all cerebral nervous system (CNS) tumors, which originate from the meningeal coverings of the brain and the spinal cord [1]
Johnson et al [63] found evidences for the activation of both the mitogen-activated protein kinase (MAPK) and the Akt/PKB pathways in meningiomas, upon growth factor receptor signaling via e.g. plateletderived growth factor BB (PDGF-BB) and PDGFβ; these authors showed that administration of MAPK or phosphatidylinositol 3-kinase (PI3K) inhibitors induces progressive growth inhibition of meningioma cells in association with reduced phosphorylation of MAPK or Akt and p70S6K, respectively
Despite the clear association observed between a more advanced tumor grade and a higher number of tumor cell clones and complex karyotypes, authors found that the pathways of intratumoral clonal evolution observed in benign meningiomas were markedly different from those most frequently found in atypical/anaplastic tumors; altogether, these results suggest that the latter tumors might not always represent a more advanced stage of www.impactjournals.com/oncotarget histologically benign meningiomas, but they could more likely correspond to stages of distinct clonal evolution pathways (Figure 2)
Summary
Meningiomas are one of the most frequent primary brain neoplasias –30-35% of all cerebral nervous system (CNS) tumors–, which originate from the meningeal coverings of the brain and the spinal cord [1]. In addition to del(6q), Pérez-Magán et al [31] reported overexpression of the histone cluster 1 genes coded at chromosome 6p (e.g. the HIST1H1c gene) in 27% and 89% of primary and recurrent meningiomas, respectively; recent results suggest that physical interaction of the H1.2 protein could be involved in epigenetic regulation of gene expression by maintaining specific DNA methylation patterns, but its functional role in meningiomas still remains to be elucidated.
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