Of all the Pol ε mutant colorectal and endometrial tumors sequenced in the TCGA studies, 15% (4/26) lacked a mutation in any mismatch repair gene and also showed no evidence of MLH1 promoter hypermethylation, demonstrating that the ultramutated phenotype can arise when mismatch repair is intact at both the genetic and epigenetic level. This evidence concerns the gene MLH1 and endometrium neoplasm.