133 BMAL1 is Upregulated in Pediatric High-Grade Gliomas

Abstract

INTRODUCTION: Pediatric high-grade gliomas (pHGG) are highly invasive brain tumors with poor survival outcomes, and novel therapeutic approaches are urgently needed. Recently, a retrospective study found timing of Temozolomide administration affects survival in adult patients with glioblastoma (Damato et al. 2021). There has, however, been limited exploration into circadian gene expression in pediatric gliomas. METHODS: We analyzed expression of BMAL1, a key circadian gene, in pediatric gliomas using bioinformatic approaches, Western blotting, and immunocytochemistry (ICC). We first compared BMAL1 expression in pLGGs and pHGGs using published publicly available data from cBioPortal for Cancer Genomics. Immunoblotting was utilized to determine BMAL1 protein expression levels in patient specimens of pHGG, pLGG and cortex from epilepsy surgery. Immunocytochemistry on synchronized primary tumor lines was used to show localization of BMAL1 protein. RESULTS: Using data from cBioPortal, we found significantly higher expression of BMAL1 in pHGGs compared to pLGGs (0.349 + 1.05 vs 0.0545 + 0.666, p < 0.001). Western blotting showed increased expression of BMAL1 in HGG tumor specimens compared to LGG and cortical specimens. Immunostaining demonstrated cellular localization of BMAL1. CONCLUSIONS: In this study, we found that the circadian gene BMAL1 is expressed in pHGGs, and that expression is higher in pHGGs compared to pLGGs and cortex. Next steps will be to understand how timing of Temozolomide in relationship to the circadian cycle affects tumor cell survival.