Figure 3.

Representation of the two serrated pathways. The sequence leading to serrated Colorectal cancer (CRC) can occur in two different molecular pathways, the sessile and the traditional serrated routes. The tumorigenic process involves progressive accumulation of specific genetic and epigenetic hits affecting normal colon epithelial cells. In the sessile serrated pathway, the transformation of the normal mucosa begins with BRAF mutations, followed by p16 and IGFBP7 promoter hypermethylation and the consequent progression toward serrated adenocarcinoma, mainly through MLH1 epigenetic alterations. In contrast, the traditional serrated pathway involves KRAS or BRAF mutations in normal colon cells which, together with MGMT or other gene methylation alterations, malignantly evolve toward traditional serrated adenoma (TSA) high-grade dysplasia and serrated adenocarcinoma (SAC).