HG-110: SINGLE-CELL TRANSCRIPTOME ANALYSIS IN PEDIATRIC HEMISPHERIC AND MIDLINE HIGH-GRADE GLIOMAS

Brain tumors are complex ecosystems containing cells with heterogeneous genotypes and phenotypes, resulting in substantial cancer cell diversity. High-grade gliomas are particularly heterogeneous tumors and currently represent the most common cause of cancer-related death in children. Increasing evidence indicates that treatment failure and resistance are at least in part due to this heterogeneity. We used single-cell RNA sequencing (scRNA-seq) to profile the transcriptome of single cells in pediatric hemispheric high-grade glioma (histone wildtype) and diffuse intrinsic pontine glioma (DIPG; H3.3 K27M mutant) and reconstructed their cellular architecture. We found restricted expression of neural stem/progenitor expression programs in distinct subsets of cells, and observed that cellular programs evolve during genetic evolution. This suggests that both genetic and superimposed developmental programs contribute to tumor heterogeneity. These results provide an unparalleled insight into the cellular composition of pediatric high-grade gliomas and DIPGs at the level of single-cell resolution, and open up new avenues for discovering novel therapeutic targets.