Novel genetic and epigenetic alterations in ... - Ous-research.no

IntroductionFigure 9. A timeline of (colorectal cancer) genetics. The left hand side of the helix (in red) lists generalgenetic hallmarks while the right hand side (in black) includes hallmarks in colorectal cancer research.Molecular and morphological developmental pathways in colorectalcancerThe adenoma-carcinoma model was first presented by Muto and co-workers in 1975[62]. Itdescribed how colorectal cancer developed through different histopathological steps, fromthe first abnormality, via increasingly dysplastic adenomas to carcinomas, and has ever sincebeen a widely accepted paradigm for colorectal carcinogenesis. In 1990, Fearon andVogelstein added genetic information to this model and suggested that alterations in at leastfour of the presented genes were sufficient for developing cancer[63]. It has later beenshown that the order of events is just as important for the cancer development as thenumber of alterations[64;65].According to the adenoma-carcinoma model, adenomas can develop into eithermicrosatellite- or chromosome instable tumors depending on the genetic makeup of thetumor[64]. Mutation in the tumor suppressor gene APC is considered to be the initiatingevent, or “gatekeeper mutation” in colorectal tumorigenesis, and has been reported25