EPCO-21. THE SPATIAL ORGANIZATION OF H3-K27M MUTANT DIFFUSE MIDLINE GLIOMA

Abstract Histone 3 lysine27-to-methionine mutant diffuse midline gliomas (H3-K27M DMGs) are among the most lethal brain tumors. Their putative cellular hierarchy has been shown to be driven by self-renewing stem-like cells arrested in an oligodendrocyte precursor-like (OPC-like) state, of which few able differentiate towards more mature astrocyte (AC)-like and (OC)-like cells. However, spatial organization underlying this tumor cell architecture its microenvironmental interactions intact H3-K27M DMG tissues remain unknown. Here, we profiled single transcriptomes 45 patient DMGs derived population-specific marker gene combinations characterize 16 tumors using targeted situ sequencing. We thereby resolved different malignant non-malignant populations including cycling, OPC-like, AC-like, OC-like, mesenchymal cells, oligodendrocytes, astrocytes, neurons, myeloid T vascular directly situ. Global neighborhood analyses indicate a higher tendency cycling OPC-like neurons localize within restricted homogeneous compartment, whereas AC-like astrocytes tend intermingle with manner. Among observed OC-like co-localize niche-like structure that is surrounded differentiated further validated niche at protein level multiplexed immunofluorescence via CODEX system. Finally, characterized relationships between consistently identifying preferred neighborhoods Together, study resolves resolution identifies local oligodendroglial lineage containing cancer thus providing novel insights into compartment suggesting potential avenues for perturbation.