Epithelial–Mesenchymal Transition and Genetically Driven Early Tumor Seedings in Extraneural Metastasis of Glioblastoma

Genetic and cell biological analyses of this rare glioblastoma (GBM) case with rapidly progressive pleural metastasis revealed essential roles of epithelial-mesenchymal transition (EMT) and glioma stem-like cells (GSCs) in extraneural metastasis. Contrary to the common prediction, the metastatic lesion shared 73% of mutations and two fusion genes with the primary but not the recurrent tumor, indicating that extraneural metastasis occurs early in GBM progression. Functional assays using primary tumor-derived GSCs confirmed EMT-enhanced migratory behaviors. EMT and genetically driven early tumor seedings are crucial for extraneural GBM metastasis, emphasizing the need for further investigation into EMT pathways and GSC biology.