Interestingly, in the aforementioned studies, 16 of 17 patients [41] and 91.2% of the 58 hypermutated patients [40] had MMR gene mutations, likely suggesting that TMZ-treated gliomas that gain MMR inactivation mutations, universally evolve to hypermutated recurrent tumors, while those lacking these potential driver mutations resulted in non-hypermutant recurrent tumors. Here, MRC1 is linked to central nervous system cancer.