Differential gene expression analysis in French bulldog high grade oligodendroglioma: breed-associated differences in tumor and tumor microenvironment gene expression

Abstract Background Several canine breeds, including boxers, Boston terriers, and French bulldogs, belong to the same phylogenetic clade and have a higher risk for high-grade oligodendroglioma (HGO) than the general canine population. Despite their shared increased risk for HGO, French bulldogs treated with immunotherapy have experienced worse survival outcomes compared to boxers and Boston terriers. We hypothesized that the French bulldog HGO transcriptome differs from those of boxers and Boston terriers, which might account for the disparity in survival. We performed RNA sequencing on formalin-fixed, paraffin-embedded tissue from French bulldogs, boxers, and Boston terriers to identify differentially expressed genes (DEGs) between French bulldogs and the other evaluated breeds. Results There were 31 DEGs in HGO samples from French bulldogs compared to boxers and Boston terriers. Gene set enrichment analysis revealed activated enrichment of 15 cell cycle progression, oncogene, and immune pathways, including E2F targets, mTOR signaling, IL2-STAT 5 signaling, and allograft rejection. Conclusions These data confirm the presence of breed-specific canine HGO transcriptomes that can be used to advance our understanding of canine glioma, its translational capacity for human glioma, and precision-based therapies for individual canine patients.