Colon
Molecular
Serrated pathway
Author: Shilpa Jain, M.D.
Last author update: 1 August 2010
Last staff update: 30 September 2020
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: CpG island methylation [title] pathway
Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Etiology | Diagrams / tables | Prognostic factorsCite this page: Jain S. Serrated pathway. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colontumormolecularCpG.html. Accessed April 19th, 2024.
Definition / general
- CpG islands (also called CG islands, p indicates a phosphodiester bond connecting the C and G) are 500 to 2000 base pair regions rich in cytosine-guanosine dinucleotide repeats, present at 5' region in 50% of human genes (Wikipedia, Web-books)
- Methylation of cytosine residues in promoter regions and proximal exons of these islands represses transcription
- Hypermethylation of the CpG dinucleotide in the promoter regions of TP16 and CDH1 tumor suppressor genes is the mechanism to inactivate these genes
- Promoter methylation of MLH1 may also occur
Terminology
- Also called epigenetic changes / epigenetic silencing
Epidemiology
- 30% of carcinomas have CpG island methylator phenotype (CIMP+)
- Patients are usually female, have more advanced age, and have smoking history
Sites
- Occurs predominantly in proximal colon
Etiology
- An important mechanism of inactivating tumor suppressor genes in the chromosomal and microsatellite instability pathways (Curr Mol Med 2006;6:401, Cancer Metastasis Rev 2004;23:29)
- However, CpG methylation can also act independently of chromosomal instability and microsatellite instability
Diagrams / tables
Images hosted on other servers:
DNA methylation
Prognostic factors
- Although controversial, recent studies suggest that CIMP status is an independent predictor of a low colon cancer specific mortality and survival advantage and a high response rate to 5-fluorouracil based treatments (Gut 2009;58:90, Int J Clin Oncol 2008;13:498), although further studies are required
