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Journal of Neuro-Oncology

, Volume 139, Issue 2, pp 469–478 | Cite as

Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design

  • Richard G. Everson
  • Yuuri Hashimoto
  • Jacob L. Freeman
  • Tiffany R. Hodges
  • Jason Huse
  • Shouhao Zhou
  • Joanne Xiu
  • David Spetzler
  • Nader Sanai
  • Lyndon Kim
  • Santosh Kesari
  • Andrew Brenner
  • Franco De Monte
  • Amy HeimbergerEmail author
  • Shaan M. Raza
Clinical Study

Abstract

Introduction

Surgery and radiation therapy are the standard treatment options for meningiomas, but these treatments are not always feasible. Expression profiling was performed to determine the presence of therapeutic actionable biomarkers for prioritization and selection of agents.

Methods

Meningiomas (n = 115) were profiled using a variety of strategies including next-generation sequencing (592-gene panel: n = 14; 47-gene panel: n = 94), immunohistochemistry (n = 8–110), and fluorescent and chromogenic in situ hybridization (n = 5–70) to determine mutational and expression status.

Results

The median age of patients in the cohort was 60 years, with a range spanning 6–90 years; 52% were female. The most frequently expressed protein markers were EGFR (93%; n = 44), followed by PTEN (77%; n = 110), BCRP (75%; n = 8), MRP1 (65%, n = 23), PGP (62%; n = 84), and MGMT (55%; n = 97). The most frequent mutation among all meningioma grades occurred in the NF2 gene at 85% (11/13). Recurring mutations in SMO and AKT1 were also occasionally detected. PD-L1 was expressed in 25% of grade III cases (2/8) but not in grade I or II tumors. PD-1 + T cells were present in 46% (24/52) of meningiomas. TOP2A and thymidylate synthase expression increased with grade (I = 5%, II = 22%, III = 62% and I = 5%, II = 23%, III = 47%, respectively), whereas progesterone receptor expression decreased with grade (I = 79%, II = 41%, III = 29%).

Conclusion

If predicated on tumor expression, our data suggest that therapeutics directed toward NF2 and TOP2A could be considered for most meningioma patients.

Keywords

Meningioma Molecular profiling NGS NF2 TOP2A PD-1 

Notes

Acknowledgements

We thank Audria Patrick and David M. Wildrick, Ph.D., for editorial assistance.

Author contributions

Concept and design: Amy B. Heimberger, Joanne Xiu, David Spetzler. Acquisition of data: Joanne Xiu and David Spetzler. Analysis and interpretation of data: Richard G. Everson, Yuuri Hashimoto, Jason Huse, Shouhao Zhou, Joanne Xiu, David Spetzler, Amy Heimberger, Shaan M. Raza. Writing, review, and/or revision of the manuscript: Richard G. Everson, Yuuri Hashimoto, Jacob L. Freeman, Tiffany R. Hodges, Jason Huse, Shouhao Zhou, Joanne Xiu, David Spetzler, Nader Sanai, Lyndon Kim, Santosh Kesari, Andrew Brenner, Franco De Monte, Amy Heimberger, Shaan M. Raza. Study supervision: David Spetzler, Amy B. Heimberger, Shaan M. Raza. All authors reviewed the manuscript and approved the final version.

Funding

This study was supported by NIH Grants P30CA16672, CA1208113 and by provost funds provided by Ethan Dmitrovsky.

Compliance with ethical standards

Conflict of interest

ABH serves on the Caris Life Sciences Scientific Advisory Board and is a stockholder in the company. JX is an employee and DS is President of Caris Life Sciences.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Richard G. Everson
    • 1
  • Yuuri Hashimoto
    • 1
  • Jacob L. Freeman
    • 1
  • Tiffany R. Hodges
    • 1
  • Jason Huse
    • 2
  • Shouhao Zhou
    • 3
  • Joanne Xiu
    • 4
  • David Spetzler
    • 4
  • Nader Sanai
    • 5
  • Lyndon Kim
    • 6
  • Santosh Kesari
    • 7
  • Andrew Brenner
    • 8
  • Franco De Monte
    • 1
  • Amy Heimberger
    • 1
    Email author
  • Shaan M. Raza
    • 1
  1. 1.Department of NeurosurgeryThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of PathologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of BiostatisticsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Caris Life SciencesPhoenixUSA
  5. 5.Division of Neurosurgical OncologyBarrow Neurological InstitutePhoenixUSA
  6. 6.Sidney Kimmel Medical College at Thomas Jefferson UniversityPhiladelphiaUSA
  7. 7.John Wayne Cancer Institute at ProvidenceSanta MonicaUSA
  8. 8.Cancer Treatment Research CenterUniversity of Texas Health Science CenterSan AntonioUSA

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