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Colon tumor

Molecular pathways

CpG island methylation pathway


Reviewers: Shilpa Jain, M.D, New York University (see Reviewers page)
Revised: 9 November 2013, last major update August 2010
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition / General
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● 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

DNA methylation

Terminology
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● Also called epigenetic changes / epigenetic silencing

Epidemiology
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● 30% of carcinomas have CpG island methylator phenotype (CIMP+)
● Patients are usually female, have more advanced age, and have smoking history

Sites
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● Occurs predominantly in proximal colon

Etiology
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● 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

Prognostic factors
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● 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

End of Colon tumor > Molecular pathways > CpG island methylation pathway


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