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Senescence and serration: a new twist to an old tale
- Source :
- The Journal of pathology. 210(2)
- Publication Year :
- 2006
-
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.
- Subjects :
- Genetics
Senescence
CpG Island Methylator Phenotype
Microsatellite instability
Intestinal Polyps
Context (language use)
Oncogenes
Biology
Cell cycle
medicine.disease_cause
medicine.disease
digestive system diseases
Pathology and Forensic Medicine
Genes, cdc
Cell Transformation, Neoplastic
Mutation
medicine
Cancer research
Gene silencing
Nevus
Humans
Carcinogenesis
Colorectal Neoplasms
neoplasms
Cellular Senescence
Subjects
Details
- ISSN :
- 00223417
- Volume :
- 210
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The Journal of pathology
- Accession number :
- edsair.doi.dedup.....e05bc00117922367fdee05f27557b5e7