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Gene & Protein in Disease Pediatric glioma circadian clock genes

particularly dangerous when they metastasize, forming that are currently being tested as acting through core
secondary tumors in the meninges and elsewhere. 107 circadian clock genes could also prove effective in treating
As described in an extensive review of GSCs in pediatric GBM and LG tumors. The lack of PER2 and
medulloblastomas, GSCs are present in all four PER3 repression in pediatric GBM and LG tumors, along
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medulloblastoma subtypes, and distinguishable GSC with other differences, suggests that an alternative drug
categories are present. For example, cells expressing development approach specific for pediatric gliomas may
be needed. The overexpression of TIMELESS in all three
either of the GSC markers CD133 and CD114 appear as glioma categories indicates another possible path for
distinct cell populations. Anticancer treatments acting effective drug development. Finally, the higher clock gene
through epigenetic modifications of genes that maintain expression in MB tumors detected in the Group 3 and
stemness are being tested, particularly histone deacetylase Group 4 subtypes, and with adolescent onset, may provide
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inhibitors. Organoid cultures have been developed to opportunities for specialized treatments.
address the role of GSCs in medulloblastoma and other
pediatric gliomas. Acknowledgments

4.5. Limitations of the current study and future We thank the additional graduate and undergraduate
directions for exploration researchers who participated in useful discussions, that
The present study preliminarily explored circadian clock were valuable contributions to this study.
gene expression in some of the most common pediatric Funding
gliomas, embarking on a journey to address the knowledge
gap. It is important to continue this approach by examining Support for this project was provided internally by Bowling
additional samples from DIPG, currently known as Green State University through assistance with computer
diffuse midline glioma (DMG), which is a pHGG that is technology.
histologically similar to GBM, highly lethal, and has Conflict of interest
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poor treatment options. DIPG is often medically treated
like GBM, resulting in poor outcomes, but is distinctly The authors declare that they have no competing interests.
different and is reported to consist of three subgroups.
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Our preliminary results suggest that some of the clinically Author contributions
relevant differences between pediatric GBM and DIPG Conceptualization: All authors
may be their differential expression of circadian clock Investigation: Austin Tyler Vogt, Veda Sanjay Mohite,
genes. Michael Eric Geusz
Some medications that target glioma subtypes are Methodology: All authors
being tested, such as against the SSH MB subtype. It may Writing – original draft: Austin Tyler Vogt, Veda Sanjay
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be useful to further target subtypes by exploiting their Mohite, Michael Eric Geusz
differences in clock gene expression and potential for Writing – review & editing: All authors
circadian rhythmicity, as suggested by the current study. Ethics approval and consent to participate
Most importantly, because of the daily oscillations in
activity of members of the circadian gene set, they should Not applicable.
be evaluated in respect to the time of day when samples
were collected and, perhaps, at some future point, the Consent for publication
phase of circadian clocks assayed in situ within patient Not applicable. All datasets were derived from data
tumors. More detailed proteomics of the oscillating clock repositories available to the public.
components within tumors is also needed because of the
many post-transcriptional effects that can impact circadian Availability of data
rhythms. 111 Original data used in this study can be obtained from the

5. Conclusion GlioVis data portal for visualization and analysis of brain
tumor expression datasets (http://gliovis.bioinfo.cnio.es/),
Pediatric and adult gliomas show some similarity in their the TIMER2.0 website, (http://timer.comp-genomics.org/
expression of core and related circadian clock genes. CRY2 timer/), GEO (https://www.ncbi.nlm.nih.gov/geo/info/
and RORB are the two core clock genes that are suppressed geo2r.html), and the University of California, Santa Cruz
in all three glioma categories: adult GBM, pediatric Cell Explorer website (https://www.pneuroonccellatlas.
GBM, and LG glioma. Consequently, pharmaceuticals org/). The collected and analyzed data are available from

Volume 4 Issue 2 (2025) 18 doi: 10.36922/gpd.4112