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

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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.

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Acknowledgements

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

Funding

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

Author information

Authors and Affiliations

  1. Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Richard G. Everson, Yuuri Hashimoto, Jacob L. Freeman, Tiffany R. Hodges, Franco De Monte, Amy Heimberger & Shaan M. Raza

  2. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jason Huse

  3. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Shouhao Zhou

  4. Caris Life Sciences, Phoenix, AZ, USA

    Joanne Xiu & David Spetzler

  5. Division of Neurosurgical Oncology, Barrow Neurological Institute, Phoenix, AZ, USA

    Nader Sanai

  6. Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA

    Lyndon Kim

  7. John Wayne Cancer Institute at Providence, Santa Monica, CA, USA

    Santosh Kesari

  8. Cancer Treatment Research Center, University of Texas Health Science Center, San Antonio, TX, USA

    Andrew Brenner

Author notes

  1. Richard G. Everson and Yuuri Hashimoto are co-lead authors.

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    1. Richard G. Everson
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    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.

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    Correspondence to Amy Heimberger.

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    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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    Everson, R.G., Hashimoto, Y., Freeman, J.L. et al. Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design. J Neurooncol 139, 469–478 (2018). https://doi.org/10.1007/s11060-018-2891-8

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