Abstract 1144: Glioblastoma cells increase expression of neurodevelopmental programs and synaptic connectivity in the tumor periphery

Abstract

Abstract Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by concomitant and adjuvant temozolomide chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the brain parenchyma, where they give rise to the recurrent tumor. Based on gene expression, the tumor core can be subtyped into mesenchymal, proneural and classical areas, each being associated with differences in genetic alterations and cellular composition. In contrast, the tumor periphery where migrating tumor cells infiltrate brain parenchyma is less characterized in patients. Using spatial transcriptomics (n = 11), we show that specific malignant states colocalize in tumor core areas with necrosis and microvascular proliferation. Malignant cells within proneural or mesenchymal subtyped cores displayed, as expected, many differences in genetic expression, although such differences disappeared in the tumor periphery. Malignant cells residing in the tumor periphery had increased expression of genes related to neurodevelopmental pathways and synaptic connectivity. Our findings show similarities in cellular states across tumor subtypes with implications for post-operative treatment and provide an updated view of the spatial landscape of glioblastomas. Citation Format: Dylan Harwood, Vilde Pedersen, Nicolai S. Bager, Ane Y. Schmidt, Tobias O. Stannius, Ausrine Areskeviciute, Knud Josefsen, Dorte S. Nørøxe, David Scheie, Hannah E. Rostalski, Ulrik Lassen, Frederik O. Bagger, Joachim Weischenfeldt, Dieter H. Heiland, Kristoffer Vitting-Seerup, Signe R. Michaelsen, Bjarne W. Kristensen. Glioblastoma cells increase expression of neurodevelopmental programs and synaptic connectivity in the tumor periphery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1144.