These findings suggest that MMR-deficient subclones pre-exist in some gliomas before TMZ treatment, while TMZ is not the cause of MMR deficiency, and the selection pressure for MMR-deficient cells is not very strong as well; otherwise, the MMR-deficient subclones would not disappear once they emerged and would expand rapidly to dominate the tumor’s clonal structure. Here, MRC1 is linked to central nervous system cancer.