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Fig. 5 | Acta Neuropathologica Communications

Fig. 5

From: Global activation of oncogenic pathways underlies therapy resistance in diffuse midline glioma

Fig. 5

Models of invasion, pathway activation and therapeutic targeting in DIPG. a. Histologic invasion pathways include the common ponto-cerebellar dissemination pathway, shown in red, and the more specific centrifugal and CSF/leptomeningeal pathways shown in blue and green, respectively. The green circle indicates the cerebellar tumor as the most common origin of supratentorial CSF seeding. b. Spatial color-coded CNV-tracking of invasive neoplastic populations within the F5 tumor that showed histologic centrifugal migration pattern. Contiguous neoplastic populations are indicated with line tracings, and isolated foci sharing the same CNV composition, with circles. Cerebellar bars indicate bilateral spread of the respective population. The corresponding color-coded CNVs are indicated in bold for gains, and regular font, for losses. c. Schematic model of epigenetic changes targeting histone H3 K27 residue. The histone H2A/H2B/H3/H4 nucleosome is represented as a blue barrel, the DNA, as a red thread, and the N-terminal histone H3 “tail”, as a black curved line. The methyl and acetyl groups are shown in orange and green, respectively. The stop sign shows blockage of enzymatic or transcriptional activity. d. Pathway activation and drug targeting model in DIPG. The oncogenic H3 K27M driver protein and mediators with dual tumor suppressor or oncogenic roles depending on context are shown in red and purple, respectively. Otherwise, the oncogenic and the tumor suppressor proteins are shown on left and right, respectively. The pathways are shown in bold font, and red and blue indicate activation or suppression, respectively. The candidate targets for therapy are underlined

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