Using the experimental design previously published (Cancer Cell, 2011, 19:305) we have developed additional GEMMs with different survival characteristics and tumor genetics. The properties and similarities of these models to human disease are being investigated at the histological as well as at the molecular levels. Importantly, our GEMM tumors recapitulate both the proneural and mesenchymal gene expression subgroups noted in human high-grade gliomas. We are interested in uncovering the molecular determinants of these subgroup differences as well as their signaling pathway characteristics. High-grade gliomas are highly infiltrative and aggressive tumors, a feature which is correlated with the lethality of these tumors and is replicated in our GEMMs. We are investigating the characteristics of infiltrating tumor cells in our models to better understand these processes and to determine if the biology of these highly active cells is different from the primary tumor mass.
Pseudopalisading Necrosis in Mouse High-Grade Gliomas. Hematoxylin and eosin staining of mouse brains reveals tumors with pseudopalisading necrosis, a feature of grade 4 tumors.