Comprehensive Molecular Profiling Identifies FOXM1 as a Key Transcription Factor for Meningioma Proliferation
- Vasudevan, Harish N;
- Braunstein, Steve E;
- Phillips, Joanna J;
- Pekmezci, Melike;
- Tomlin, Bryan A;
- Wu, Ashley;
- Reis, Gerald F;
- Magill, Stephen T;
- Zhang, Jie;
- Feng, Felix Y;
- Nicholaides, Theodore;
- Chang, Susan M;
- Sneed, Penny K;
- McDermott, Michael W;
- Berger, Mitchel S;
- Perry, Arie;
- Raleigh, David R
- et al.
Published Web Location
https://www.sciencedirect.com/science/article/pii/S2211124718303425?via=ihubAbstract
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.
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