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Senescence and serration: a new twist to an old tale
Author(s) -
Minoo P,
Jass JR
Publication year - 2006
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2047
Subject(s) - senescence , carcinogenesis , biology , microsatellite instability , cancer research , kras , telomere , phenotype , dna methylation , gene silencing , oncogene , genetics , cell cycle , mutation , cancer , gene , gene expression , allele , microsatellite
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.