Serrated polyps, which are the immediate precursors to CIMP tumors, evolve through activation of the MAPK-ERK pathway by BRAF/KRAS mutations and are distinguished by methylation-mediated transcriptional inactivation of various genes that belong to the β-catenin/WNT pathway (SFRP family, CDX2, and MCC), the insulin-like growth factor signaling pathway (IGFBP7), cell-cycle control proteins (CDKN2A), and the DNA mismatch repair (MLH-1) family36,37, CIMP-positive CRC shows DNA hypermethylation of the MLH1 mismatch repair gene, 38 and is highly enriched for the BRAF V600E-activating mutation. Here, BRAF is linked to colorectal carcinoma.