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

doi:10.1016/j.celrep.2018.03.013

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 journal › Article › peer-review

58 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 language	English (US)
Pages (from-to)	3672-3683
Number of pages	12
Journal	Cell reports
Volume	22
Issue number	13
DOIs	https://doi.org/10.1016/j.celrep.2018.03.013
State	Published - Mar 27 2018
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2018.03.013

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Vasudevan, H. N., Braunstein, S. E., Phillips, J. J., Pekmezci, M., Tomlin, B. A., Wu, A., Reis, G. F., Magill, S. T., Zhang, J., Feng, F. Y., Nicholaides, T., Chang, S. M., Sneed, P. K., McDermott, M. W., Berger, M. S., Perry, A., & Raleigh, D. R. (2018). Comprehensive Molecular Profiling Identifies FOXM1 as a Key Transcription Factor for Meningioma Proliferation. Cell reports, 22(13), 3672-3683. https://doi.org/10.1016/j.celrep.2018.03.013

@article{8cb8f997b11a40e3b2176676166a7cab,

title = "Comprehensive Molecular Profiling Identifies FOXM1 as a Key Transcription Factor for Meningioma Proliferation",

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.",

keywords = "DNA methylation, FOXM1, NF2, RNA sequencing, Wnt, epigenome, genome, meningioma, transcriptome, whole-exome sequencing",

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

note = "Funding Information: We thank David Solomon, MD, PhD, for providing Ben-Men-1 and HBL-52 primary meningioma cell lines. The University of California, San Francisco, Brain Tumor SPORE Biospecimen and Pathology Core provided tissue, TMAs, and histologic services ( NIH grant P50CA097257 ). This work was supported by grants from the Linda Wolfe Meningioma Research Fund , the Goddard Foundation , and the University of California, San Francisco, Physician Scientist Scholar Program to D.R.R. and from the NIH ( 1F32CA213944-01 ) to S.T.M. Funding Information: We thank David Solomon, MD, PhD, for providing Ben-Men-1 and HBL-52 primary meningioma cell lines. The University of California, San Francisco, Brain Tumor SPORE Biospecimen and Pathology Core provided tissue, TMAs, and histologic services (NIH grant P50CA097257). This work was supported by grants from the Linda Wolfe Meningioma Research Fund, the Goddard Foundation, and the University of California, San Francisco, Physician Scientist Scholar Program to D.R.R. and from the NIH (1F32CA213944-01) to S.T.M. Publisher Copyright: {\textcopyright} 2018",

year = "2018",

month = mar,

day = "27",

doi = "10.1016/j.celrep.2018.03.013",

language = "English (US)",

volume = "22",

pages = "3672--3683",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "13",

}

Vasudevan, HN, Braunstein, SE, Phillips, JJ, Pekmezci, M, Tomlin, BA, Wu, A, Reis, GF, Magill, ST, Zhang, J, Feng, FY, Nicholaides, T, Chang, SM, Sneed, PK, McDermott, MW, Berger, MS, Perry, A & Raleigh, DR 2018, 'Comprehensive Molecular Profiling Identifies FOXM1 as a Key Transcription Factor for Meningioma Proliferation', Cell reports, vol. 22, no. 13, pp. 3672-3683. https://doi.org/10.1016/j.celrep.2018.03.013

TY - JOUR

T1 - Comprehensive Molecular Profiling Identifies FOXM1 as a Key Transcription Factor for Meningioma Proliferation

AU - Vasudevan, Harish N.

AU - Braunstein, Steve E.

AU - Phillips, Joanna J.

AU - Pekmezci, Melike

AU - Tomlin, Bryan A.

AU - Wu, Ashley

AU - Reis, Gerald F.

AU - Magill, Stephen T.

AU - Zhang, Jie

AU - Feng, Felix Y.

AU - Nicholaides, Theodore

AU - Chang, Susan M.

AU - Sneed, Penny K.

AU - McDermott, Michael W.

AU - Berger, Mitchel S.

AU - Perry, Arie

AU - Raleigh, David R.

N1 - Funding Information: We thank David Solomon, MD, PhD, for providing Ben-Men-1 and HBL-52 primary meningioma cell lines. The University of California, San Francisco, Brain Tumor SPORE Biospecimen and Pathology Core provided tissue, TMAs, and histologic services ( NIH grant P50CA097257 ). This work was supported by grants from the Linda Wolfe Meningioma Research Fund , the Goddard Foundation , and the University of California, San Francisco, Physician Scientist Scholar Program to D.R.R. and from the NIH ( 1F32CA213944-01 ) to S.T.M. Funding Information: We thank David Solomon, MD, PhD, for providing Ben-Men-1 and HBL-52 primary meningioma cell lines. The University of California, San Francisco, Brain Tumor SPORE Biospecimen and Pathology Core provided tissue, TMAs, and histologic services (NIH grant P50CA097257). This work was supported by grants from the Linda Wolfe Meningioma Research Fund, the Goddard Foundation, and the University of California, San Francisco, Physician Scientist Scholar Program to D.R.R. and from the NIH (1F32CA213944-01) to S.T.M. Publisher Copyright: © 2018

PY - 2018/3/27

Y1 - 2018/3/27

N2 - 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.

AB - 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.

KW - DNA methylation

KW - FOXM1

KW - NF2

KW - RNA sequencing

KW - Wnt

KW - epigenome

KW - genome

KW - meningioma

KW - transcriptome

KW - whole-exome sequencing

UR - http://www.scopus.com/inward/record.url?scp=85044138663&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044138663&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.03.013

DO - 10.1016/j.celrep.2018.03.013

M3 - Article

C2 - 29590631

AN - SCOPUS:85044138663

SN - 2211-1247

VL - 22

SP - 3672

EP - 3683

JO - Cell Reports

JF - Cell Reports

IS - 13

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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