MRC1 and central nervous system cancer: When gliomas are challenged with TMZ, recurrent subclones often emerge with inactivating mutations in genes encoding DNA mismatch repair (MMR) enzymes, most commonly MSH2, MSH6, MLH1, and PMS2. Loss of function in these genes leads to failure of MMR mechanisms, which is essential for inducing programmed cell death in tumor cells damage by temozolomide, thus contributing to temozolomide resistance in recurrent tumors [6, 12, 30].