POLE and glioblastoma: As a glioblastoma patient from our index family (patient Fam011-III.1/M1) and a glioblastoma patient previously described [31], both carrying rare POLE germline variants, developed spinal metastases, we performed POLE mutational analysis in three other patients with glioblastoma CNS WHO grade 4 and spinal metastasis (patients M2-M4, Fig. 2a).