In sporadic cancers, a DNA repair deficiency is occasionally found to be due to a mutation in a DNA repair gene.  However, much more frequently, reduced or absent expression of a DNA repair gene in cancer is due to methylation of its promoter.  For example, of 113 colorectal cancers examined, only four had a missense mutation in the DNA repair gene MGMT, while the majority had reduced MGMT expression due to methylation of the MGMT promoter region.  Similarly, among 119 cases of mismatch repair-deficient colorectal cancers that lacked DNA repair gene PMS2 expression, 6 had a mutation in the PMS2 gene, while for 103 PMS2 was deficient because its pairing partner MLH1 was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1).  In the remaining 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the microRNA, miR-155, which down-regulates MLH1.