Comprehensive Molecular Profiling Identifies FOXM1 as a Key Transcription Factor for Meningioma Proliferation

Harish N. Vasudevan, Steve E. Braunstein, Joanna J. Phillips, Melike Pekmezci, Bryan A. Tomlin, Ashley Wu, Gerald F. Reis, Stephen T. Magill, Jie Zhang, Felix Y. Feng, Theodore Nicholaides, Susan M. Chang, Penny K. Sneed, Michael W. McDermott, Mitchel S. Berger, Arie Perry, David R. Raleigh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Meningioma is the most common primary intracranial tumor, but the molecular drivers of aggressive meningioma are incompletely understood. Using 280 human meningioma samples and RNA sequencing, immunohistochemistry, whole-exome sequencing, DNA methylation arrays, and targeted gene expression profiling, we comprehensively define the molecular profile of aggressive meningioma. Transcriptomic analyses identify FOXM1 as a key transcription factor for meningioma proliferation and a marker of poor clinical outcomes. Consistently, we discover genomic and epigenomic factors associated with FOXM1 activation in aggressive meningiomas. Finally, we define a FOXM1/Wnt signaling axis in meningioma that is associated with a mitotic gene expression program, poor clinical outcomes, and proliferation of primary meningioma cells. In summary, we find that multiple molecular mechanisms converge on a FOXM1/Wnt signaling axis in aggressive meningioma. Using multiplatform molecular profiling, Vasudevan et al. comprehensively define the molecular profile of aggressive meningioma. They identify genomic, epigenomic, and transcriptomic mechanisms that converge on a FOXM1/Wnt signaling axis in aggressive meningioma that is associated with meningioma cell proliferation and is a marker of poor clinical outcomes across molecular subgroups.

Original languageEnglish (US)
Pages (from-to)3672-3683
Number of pages12
JournalCell reports
Volume22
Issue number13
DOIs
StatePublished - Mar 27 2018
Externally publishedYes

Keywords

  • DNA methylation
  • FOXM1
  • NF2
  • RNA sequencing
  • Wnt
  • epigenome
  • genome
  • meningioma
  • transcriptome
  • whole-exome sequencing

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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