Intraventricular meningiomas frequently harbor NF2 mutations but lack common genetic alterations in TRAF7, AKT1, SMO, KLF4, PIK3CA, and TERT

Acta Neuropathol Commun. 2019 Aug 30;7(1):140. doi: 10.1186/s40478-019-0793-4.

Abstract

Intraventricular meningiomas (IVMs) account for less than 5% of all intracranial meningiomas; hence their molecular phenotype remains unknown. In this study, we were interested whether genetic alterations in IVMs differ from meningiomas in other locations and analyzed our institutional series with respect to clinical and molecular characteristics. A total of 25 patients with surgical removal of an IVM at our department between 1986 and 2018 were identified from our institutional database. Median progression-free survival (PFS) was 79 months (range of 2-319 months) and PFS at 5 years was 86%. Corresponding tumor tissue was available for 18 patients including one matching recurrence and was subjected to targeted panel sequencing of 130 selected genes frequently mutated in brain cancers by applying a custom hybrid capture approach on a NextSeq500 instrument. Loss of chromosome 22q and 1p occurred frequently in 89 and 44% of cases. Deleterious NF2 mutations were found in 44% of IVMs (n = 8/18). In non-NF2-mutated IVMs, previously reported genetic alterations including TRAF7, AKT1, SMO, KLF4, PIK3CA, and TERT were lacking, suggesting alternative genes in the pathogenesis of non-NF2 IVMs. In silico analysis revealed possible damaging mutations of APC, GABRA6, GSE1, KDR, and two SMO missense mutations differing from previously reported ones. Interestingly, all WHO°II IVMs (n = 3) harbored SMARCB1 and SMARCA4 mutations, indicating a role of the SWI/SNF chromatin remodeling complex in aggressive IVMs.

Keywords: Intraventricular meningioma; NF2; SMARCA4; SMARCB1; Targeted panel sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cerebral Ventricle Neoplasms / diagnostic imaging
  • Cerebral Ventricle Neoplasms / genetics*
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Cohort Studies
  • Female
  • Humans
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Male
  • Meningeal Neoplasms / diagnostic imaging
  • Meningeal Neoplasms / genetics*
  • Meningioma / diagnostic imaging
  • Meningioma / genetics*
  • Middle Aged
  • Mutation / genetics*
  • Neurofibromin 2 / genetics*
  • Proto-Oncogene Proteins c-akt / genetics
  • Retrospective Studies
  • Smoothened Receptor / genetics
  • Telomerase / genetics
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / genetics
  • Young Adult

Substances

  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • NF2 protein, human
  • Neurofibromin 2
  • SMO protein, human
  • Smoothened Receptor
  • TRAF7 protein, human
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • TERT protein, human
  • Telomerase