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In this model, conversion from a senescent nevus to a malignant melanoma is accompanied by loss of expression of p16. Serrated polyps of the colorectum may provide a further example of oncogene\u2010induced senescence. <jats:italic>BRAF<\/jats:italic> and <jats:italic>KRAS<\/jats:italic> mutation may initiate different pathways of senescence\u2010associated serrated neoplasia in the colorectum, the former linked to CpG island methylator phenotype (CIMP)\u2010high (CIMP1) and microsatellite instability (MSI)\u2010high status and the latter with CIMP\u2010low (CIMP2) and MSI\u2010low status. The role of methylation in both Raf\u2010 and Ras\u2010associated pathways is to drive tumorigenesis by silencing pro\u2010apoptotic and cell cycle inhibitory genes. Both pathways are associated with mutation of <jats:italic>Ras\u2010induced senescence 1<\/jats:italic> (<jats:italic>RIS1<\/jats:italic>), but the biological role of <jats:italic>RIS1<\/jats:italic> requires further elucidation. Copyright \u00a9 2006 Pathological Society of Great Britain and Ireland. 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