Serrated pathway

Topic Completed: 1 August 2010

Minor changes: 30 September 2020

Copyright: 2003-2021,, Inc.

PubMed Search: CpG island methylation [title] pathway

Shilpa Jain, M.D.
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Cite this page: Jain S. Serrated pathway. website. Accessed October 25th, 2021.
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
  • Also called epigenetic changes / epigenetic silencing
  • 30% of carcinomas have CpG island methylator phenotype (CIMP+)
  • Patients are usually female, have more advanced age, and have smoking history
  • Occurs predominantly in proximal colon
  • 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

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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
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