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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

Cite this page: Jain S. Serrated pathway. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colontumormolecularCpG.html. Accessed December 30th, 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

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