Previous study demonstrated that CIMP+ colon tumors had a unique association with BRAFV600E oncogene mutation, and CIMP-associated methylation of MLH1 induced mismatch repair deficiency and resulted in a genomic instability status, also known as MSI, to generate more mutation burden and neoantigen (Weisenberger et al., 2006). Here, MLH1 is linked to mismatch repair cancer syndrome 1.