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

Multiplatform profiling of meningioma provides molecular insight and prioritization of drug... 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 hybridiza- tion (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 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neuro-Oncology Springer Journals

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

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Medicine & Public Health; Oncology; Neurology
ISSN
0167-594X
eISSN
1573-7373
D.O.I.
10.1007/s11060-018-2891-8
Publisher site
See Article on Publisher Site

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 hybridiza- tion (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

Journal

Journal of Neuro-OncologySpringer Journals

Published: May 30, 2018

References

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