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

Cell Reports (Mar 2018)

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

Affiliations

Harish N. Vasudevan: Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA
Steve E. Braunstein: Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA
Joanna J. Phillips: Department of Pathology, University of California, San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA
Melike Pekmezci: Department of Pathology, University of California, San Francisco, San Francisco, CA, USA; Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA
Bryan A. Tomlin: Department of Economics, California State University Channel Islands, Camarillo, CA, USA
Ashley Wu: Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA
Gerald F. Reis: Department of Pathology, University of California, San Francisco, San Francisco, CA, USA
Stephen T. Magill: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA
Jie Zhang: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA
Felix Y. Feng: Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA
Theodore Nicholaides: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA
Susan M. Chang: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA
Penny K. Sneed: Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA
Michael W. McDermott: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA
Mitchel S. Berger: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA
Arie Perry: Department of Pathology, University of California, San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA
David R. Raleigh: Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Corresponding author

Journal volume & issue: Vol. 22, no. 13
pp. 3672 – 3683

Abstract

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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

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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