Pediatric CMMRD patients presenting with brain tumors commonly have biallelic loss of PSM2 or MSH6 (Bakry et al. 2014; Vasen et al. 2014; Wimmer et al. 2014), ultra-hypermutated pediatric GBM, and a unique MMR first/POLE second mutational signature (Shlien et al. 2015; Campbell et al. 2017). This evidence concerns the gene MSH6 and brain neoplasm.