Senescence and serration: a new twist to an old tale

Publisher Website
Google Scholar
Abstract
Interest in the role of oncogene‐induced senescence in tumorigenesis is mounting. Raf‐associated senescence in cutaneous nevi has been advanced as an example of this process occurring in the context of a human tumour. 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‐induced senescence. BRAF and KRAS mutation may initiate different pathways of senescence‐associated serrated neoplasia in the colorectum, the former linked to CpG island methylator phenotype (CIMP)‐high (CIMP1) and microsatellite instability (MSI)‐high status and the latter with CIMP‐low (CIMP2) and MSI‐low status. The role of methylation in both Raf‐ and Ras‐associated pathways is to drive tumorigenesis by silencing pro‐apoptotic and cell cycle inhibitory genes. Both pathways are associated with mutation of Ras‐induced senescence 1 (RIS1), but the biological role of RIS1 requires further elucidation. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.