Abstract
Abstract Background: Diffuse midline glioma (DMG), H3 K27-altered are highly aggressive malignancies of the central nervous system that affect both pediatric and adult populations. The immune layout and genetic changes within the tumor microenvironment associated with these high-grade malignancies are thought to play an integral role in the phenotypic differences in tumor presentation and clinical course between both populations. Comparative landscapes between pediatric and adult DMGs is not known. Methods: The NanoString GeoMxTM Digital Spatial Profiler platform was used to determine the immune marker and genetic layout in a cohort of both pediatric and adult DMG, H3 K27-altered tissue samples. Three fluorescently labeled antibodies targeting immune cells (CD45), epithelial cells (PanCK), tumor cells (H3 K27M) and a nucleic acid stain (SYTO-13) were used to identify and separate out the various components within the tumor tissues from selected regions of interest. The resultant information was then pooled into libraries that were run through the Illumina sequencing platform to assess transcriptomic and proteomic data for both cohorts of samples. Results: Our data revealed the immune and genetic expression seen within both populations across multiple regions of interest within the samples. Differences were seen specific to each population that may have clinical significance and warrant further exploration including a significant increase in genes associated with RTK pathways in the pediatric samples. Conclusion: The digital spatial analysis of pediatric and adult DMG, H3 K27-altered shows differences within the molecular landscape which may contribute to the clinical differences between both populations. These observed differences may play a role in future treatments and further research is needed to explore this. Citation Format: Sudarshawn Damodharan, Alyssa Rosenbloom, Mahua Dey. High-plex spatial multiomics of pediatric and adult diffuse midline glioma, H3 K27-altered [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2052.
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