It has been shown that MMR-deficient crypt foci are present in normal colonic mucosa of Lynch syndrome patients, but not in sporadic MSI CRC patients, with cancers arising from right-sided BRAF-mutant serrated lesions.24,44,45 A history of completely different precursor lesions in sporadic and hereditary MSI CRCs could be an explanation for a weaker immune activation in sporadic MSI CRCs compared with hereditary ones. This evidence concerns the gene BRAF and Lynch syndrome.