Spatial analysis reveals the evolving organization of IDH-mutant glioma

Here, we combine spatial transcriptomics and spatial proteomics of IDH-mutant gliomas to define organizational principles across histological grades. In low-grade tumors, spatial organization is shaped by underlying brain anatomy.

We identify a functional white–grey matter junction that restricts cortical invasion and is associated with marked changes in tumor composition and cellular phenotypes. This boundary is preferentially traversed by oligodendrocyte progenitor (OPC)-like malignant cells, suggesting a role in tumor expansion. In contrast, intermediate-grade tumors are largely disorganized, with few recurring interactions between cancer cell states and microenvironmental cell types.