Senescence and serration: a new twist to an old tale.
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.
Minoo
P
P
Department of Pathology, McGill University, Montreal, Quebec, Canada.
Jass
J R
JR
D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics; D018816:Genes, cdc; D006801:Humans; D007417:Intestinal Polyps / Q000235:genetics*; D009154:Mutation; D009857:Oncogenes / Q000235:genetics