The Same, but Different: Shared Hallmarks and Divergent Drivers in Adult, Pediatric and Canine Glioma.
7 affiliations
- 1Department of Small Animal Clinical Science, University of Liverpool, Liverpool CH64 7TE, UK.
- 2Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN 47906, USA.
- 3Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47906, USA.
- 4Department of Statistics, Purdue University, West Lafayette, IN 47906, USA.
- 5Department of Epidemiology and Biostatistics, UC Irvine, Irvine, CA 92697, USA.
- 6Cancer Data Science Initiatives, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
- 7Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47906, USA.
Abstract
Malignant gliomas are the most common primary brain tumors, with dismal outcomes. Pet dogs have been proposed as a valuable model for studying gliomas. Here, we compare spontaneously occurring gliomas from adult and pediatric human and canine patients, focusing on the tumor microenvironment (TME) and the canonical pathways of human glioma dysregulation (RTK/RAS/PI(3)K, p53 and Rb). Transcriptomic, genomic, and methylation data from adult, pediatric, and canine samples were evaluated. Across cohorts, aberrant signaling in the three canonical pathways correlated with increasing tumor grade. Canine high-grade glioma (HGG) showed extensive pathway dysregulation, especially when incorporating differentially expressed genes such as TP53. PDGFRA was a key driver of glioma in purebred brachycephalic ("short-skulled") dogs. IDH1 mutations and hypermethylation were concentrated in adult tumors. Both species exhibited increased neutrophils, M2 macrophages, and regulatory T cells, coupled with depletion of key antitumor effectors. PD-1 and PD-L1 immune checkpoint biology was similarly preserved. Canine glioma seems to occupy a "middle ground" between pediatric and adult. Methylation patterns mirrored pediatric glioma, yet immune infiltration and pathway activation resembled adult HGG. Complex heterogeneity between patients was a major similarity between species. Despite different driver mutations, dogs and humans converge on a similar malignant, immune-suppressed TME.
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BibTeX
@article{bentley2026same,
title = {{The Same, but Different: Shared Hallmarks and Divergent Drivers in Adult, Pediatric and Canine Glioma.}},
author = {R Timothy Bentley and Sagar M Utturkar and Harish Kothandaraman and Deepika Dhawan and Danni Liu and Matthew Beyers and Min Zhang and Deborah W Knapp and Nadia A Lanman},
journal = {Current oncology (Toronto, Ont.)},
year = {2026},
month = sep,
doi = {10.3390/curroncol33100592},
url = {https://europepmc.org/article/MED/42930160},
note = {CC BY},
}
RIS
TY - JOUR
TI - The Same, but Different: Shared Hallmarks and Divergent Drivers in Adult, Pediatric and Canine Glioma.
AU - R Timothy Bentley
AU - Sagar M Utturkar
AU - Harish Kothandaraman
AU - Deepika Dhawan
AU - Danni Liu
AU - Matthew Beyers
AU - Min Zhang
AU - Deborah W Knapp
AU - Nadia A Lanman
PY - 2026
DA - 2026/09/30
JO - Current oncology (Toronto, Ont.)
DO - 10.3390/curroncol33100592
UR - https://europepmc.org/article/MED/42930160
AB - Malignant gliomas are the most common primary brain tumors, with dismal outcomes. Pet dogs have been proposed as a valuable model for studying gliomas. Here, we compare spontaneously occurring gliomas from adult and pediatric human and canine patients, focusing on the tumor microenvironment (TME) and the canonical pathways of human glioma dysregulation (RTK/RAS/PI(3)K, p53 and Rb). Transcriptomic, genomic, and methylation data from adult, pediatric, and canine samples were evaluated. Across cohorts, aberrant signaling in the three canonical pathways correlated with increasing tumor grade. Canine high-grade glioma (HGG) showed extensive pathway dysregulation, especially when incorporating differentially expressed genes such as TP53. PDGFRA was a key driver of glioma in purebred brachycephalic ("short-skulled") dogs. IDH1 mutations and hypermethylation were concentrated in adult tumors. Both species exhibited increased neutrophils, M2 macrophages, and regulatory T cells, coupled with depletion of key antitumor effectors. PD-1 and PD-L1 immune checkpoint biology was similarly preserved. Canine glioma seems to occupy a "middle ground" between pediatric and adult. Methylation patterns mirrored pediatric glioma, yet immune infiltration and pathway activation resembled adult HGG. Complex heterogeneity between patients was a major similarity between species. Despite different driver mutations, dogs and humans converge on a similar malignant, immune-suppressed TME.
SN - 1198-0052
SN - 1718-7729
ER -