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

Publication Title

Journal of neuro-oncology

Authors

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, John Wayne Cancer Institute at Providence, Santa Monica, CA, USA.Follow
Andrew Brenner
Franco De Monte
Amy Heimberger
Shaan M Raza

Document Type

Article

Publication Date

5-30-2018

Keywords

Meningioma; Molecular profiling; NF2; NGS; PD-1; TOP2A

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.

Area of Special Interest

Cancer

Area of Special Interest

Neurosciences (Brain & Spine)

Specialty/Research Institute

Neurosciences

Specialty/Research Institute

Oncology