POLE and glioblastoma: The ultra-high TMB in pediatric GBM has been statistically (P < 10−13) linked with the synergistic effect of germline MMR deficiency (i.e., CMMRD) and proofreading function defect from a somatic mutation in replicating DNA polymerase POLE or PLOD1 (Shlien et al. 2015; Hodges et al. 2017).