MECOM encodes a transcriptional regulator protein, and 7.6% of CRC with MSI-H46 carry frameshift mutations in MECOM. MECOM acts as a negative feedback regulator of NFκB47, raising the possibility that loss of function mutations in Mecom can activate NFκB signaling to promote the cell cycle in the inflammatory microenvironment. Here, MECOM is linked to colorectal carcinoma.