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

oleh: 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

Format: Article
Diterbitkan: Elsevier 2018-03-01

Deskripsi

Summary: 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. Keywords: DNA methylation, epigenome, FOXM1, genome, meningioma, NF2, RNA sequencing, transcriptome, whole-exome sequencing, Wnt