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Child's Nervous System
Published in: Child's Nervous System 11/2016

01-11-2016 | Brief Communication

Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system

Authors: Simone Treiger Sredni, Chiang-Ching Huang, Mario Suzuki, Tatiana Pundy, Pauline Chou, Tadanori Tomita

Published in: Child's Nervous System | Issue 11/2016

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Abstract

Background

Pediatric low-grade gliomas (P-LGG) consist of a mixed group of brain tumors that correspond to the majority of CNS tumors in children. Notably, they may exhibit spontaneous involution after subtotal surgical removal (STR). In this study, we investigated molecular indicators of spontaneous involution in P-LGG.

Methods

We performed an integrated molecular analysis including high throughput gene expression (GE), microRNA (miRNA) expression data of primary, untreated tumors from patients with P-LGG who underwent STR at our institution, with at least 10 years follow-up.

Results

We identified a set of protein-coding genes and miRNAs significantly differentially expressed in P-LGG that presented spontaneous involution (involution—I) or without progression (stable—S) after STR alone. The cannabinoid receptor 1 (CNR1 or CB1) gene (FC = 2.374; p value = 0.007) was at the top of the list and predicted to be regulated by hsa-miR-29b-3p (FC = −2.353, p value = 0.0001). CNR1 also showed a trend to be higher expressed in S/I by immunohistochemistry.

Conclusions

The P-LGG, which remained stable or that presented spontaneous involution after STR, showed significantly higher CNR1 expression at the time of diagnosis. We hypothesize that high expression levels of CNR1 provide tumor susceptibility to the antitumor effects of circulating endocannabinoids like anandamide, resulting in tumor involution. This corroborates with reports suggesting that CNR1 agonists and activators of the endocannabinoid system may represent therapeutic opportunities for children with LGG. We also suggest that CNR1 may be a prognostic marker for P-LGG. This is the first time spontaneous involution of P-LGG has been suggested to be induced by endocannabinoids.
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Metadata
Title
Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system
Authors
Simone Treiger Sredni
Chiang-Ching Huang
Mario Suzuki
Tatiana Pundy
Pauline Chou
Tadanori Tomita
Publication date
01-11-2016
Publisher
Springer Berlin Heidelberg
Published in
Child's Nervous System / Issue 11/2016
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-016-3243-7

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