METB-03. THE DISTINCT GENOMICS OF HIGH-GRADE INFANT GLIOMAS AMONG PEDIATRIC GLIOMAS HARBORING RECEPTOR TYROSINE KINASE FUSIONS

Gliomas account for about 60% of pediatric brain tumors, about half of which are classified as high-grade. Recent studies have shown that infants with high-grade gliomas (HGG) harboring receptor tyrosine kinase (RTK) fusions have a more favorable prognosis than pediatric HGG patients. The molecular mechanisms for this favorable, but from the histology divergent clinical outcome, are yet unknown. We analyzed n=18 brain tumor samples (n=7 infant, n=11 pediatric) of patients with low-grade glioma (LGGs) or HGG presenting with RTK fusions using single-cell RNA sequencing. Considering the different fusion genes (ALK n=6, NTRK n=8, and MET n=4), age groups, and glioma grades, we evaluated the metaprograms of tumor cells and their proportions using non-negative matrix factorization. Preliminary results show similar metaprograms comparing infant and pediatric LGG. Cells detected as MES-like did not occur in LGG but were found in several HGG samples. However, in HGG, the MES-like cells show different expression patterns for infant and pediatric samples. In addition, compared with pediatric HGG, infant HGG has a higher proportion of programs that are predominantly present in LGG, such as AC-like and NPC-like. These initial findings serve as a starting point for cell type-specific transcription factor regulatory networks and are an important step toward understanding the underlying biology of this distinct pediatric brain tumor entity.