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 Heimberger, Shaan M. Raza

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalJournal of Neuro-Oncology
DOIs
StateAccepted/In press - May 30 2018

Fingerprint

Meningioma
Clinical Trials
Pharmaceutical Preparations
Genes
Thymidylate Synthase
Mutation
Progesterone Receptors
Therapeutics
Fluorescence In Situ Hybridization
Neoplasms
Radiotherapy
Biomarkers
Immunohistochemistry
T-Lymphocytes
Proteins

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design. / Everson, Richard G.; Hashimoto, Yuuri; Freeman, Jacob L.; Hodges, Tiffany R.; Huse, Jason; Zhou, Shouhao; Xiu, Joanne; Spetzler, David; Sanai, Nader; Kim, Lyndon; Kesari, Santosh; Brenner, Andrew; de Monte, Franco; Heimberger, Amy; Raza, Shaan M.

In: Journal of Neuro-Oncology, 30.05.2018, p. 1-10.

Research output: Contribution to journalArticle

Everson, RG, Hashimoto, Y, Freeman, JL, Hodges, TR, Huse, J, Zhou, S, Xiu, J, Spetzler, D, Sanai, N, Kim, L, Kesari, S, Brenner, A, de Monte, F, Heimberger, A & Raza, SM 2018, 'Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design', Journal of Neuro-Oncology, pp. 1-10. https://doi.org/10.1007/s11060-018-2891-8
Everson, Richard G. ; Hashimoto, Yuuri ; Freeman, Jacob L. ; Hodges, Tiffany R. ; Huse, Jason ; Zhou, Shouhao ; Xiu, Joanne ; Spetzler, David ; Sanai, Nader ; Kim, Lyndon ; Kesari, Santosh ; Brenner, Andrew ; de Monte, Franco ; Heimberger, Amy ; Raza, Shaan M. / Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design. In: Journal of Neuro-Oncology. 2018 ; pp. 1-10.
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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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T1 - Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design

AU - Everson, Richard G.

AU - Hashimoto, Yuuri

AU - Freeman, Jacob L.

AU - Hodges, Tiffany R.

AU - Huse, Jason

AU - Zhou, Shouhao

AU - Xiu, Joanne

AU - Spetzler, David

AU - Sanai, Nader

AU - Kim, Lyndon

AU - Kesari, Santosh

AU - Brenner, Andrew

AU - de Monte, Franco

AU - Heimberger, Amy

AU - Raza, Shaan M.

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N2 - 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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