Glioblastoma (GBM) is regarded as an aggressive brain tumor that rarely develops extracranial metastases. Despite well-investigated molecular alterations in GBM, there is a limited understanding of these associated with the metastatic potential. We herein present a case report of a 43-year-old woman with frontal GBM with primitive neuronal component who underwent gross total resection followed by chemoradiation. Five months after surgery, the patient was diagnosed with an intraspinal GBM metastasis. Next-generation sequencing analysis of both the primary and metastatic GBM tissues was performed using the Illumina TruSight Tumor 170 assay. The number of single nucleotide variants observed in the metastatic sample was more than two times higher. Mutations in TP53, PTEN, and RB1 found in the primary and metastatic tissue samples indicated the mesenchymal molecular GBM subtype. Among others, there were two inactivating mutations (Arg1026Ile, Trp1831Ter) detected in the NF1 gene, two novel NOTCH3 variants of unknown significance predicted to be damaging (Pro1505Thr, Cys1099Tyr), one novel ARID1A variant of unknown significance (Arg1046Ser), and one gene fusion of unknown significance, EIF2B5-KIF5B, in the metastatic sample. Based on the literature evidence, the alterations of NF1, NOTCH3, and ARID1A could explain, at least in part, the acquired invasiveness and metastatic potential in this particular GBM case.

1st Department of Pathology St Anne's University Hospital Brno and Faculty of Medicine Masaryk University 602 00 Brno Czech Republic

Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic

Department of Biology Faculty of Medicine and Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute and Faculty of Medicine Masaryk University 656 53 Brno Czech Republic

Department of Neurosurgery St Anne's University Hospital Brno and Faculty of Medicine Masaryk University 602 00 Brno Czech Republic

Department of Radiation Oncology Masaryk Memorial Cancer Institute Brno and Faculty of Medicine Masaryk University 656 53 Brno Czech Republic

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Breaking boundaries: role of the brain barriers in metastatic process