MRC1 and neoplasm: According to the model described by Knudson et al. for tumor suppressor genes such as MMR genes, one allele of the MMR gene has a germline mutation (first hit) and the second allele of the same MMR gene is inactivated at the somatic level (second hit) by various alterations (somatic mutation, genomic rearrangement, promoter hypermethylation, and loss of heterozygosity), which induce deficiency of the MMR system [41].