Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Tissue of Origin Determines Cancer-associated CpG Island Promoter Hypermethylation Patterns

Published: Friday, October 05, 2012
Last Updated: Friday, October 05, 2012
Bookmark and Share
Meehan, Sproul and co-workers conclude that general aberrant promoter hypermethylation in cancer does not promote tumorigenesis, but instead reinforces transcription repression inherited from pre-cancerous tissue.

It has been proposed that DNA methylation of tumour suppressor genes is a key event in carcinogenesis, driving cells to become cancer cells. In previous work (PMID: 21368160), the authors could not identify de novo methylated genes in breast cancer that fitted with this view. Instead they implicated aberrant DNA methylation as a marker of cell lineage rather than tumour progression.  In most cases, DNA methylation did not appear to cause the repression with which it is associated. In their present work they extended this observation to 6 additional tumour types. Their recent analysis supports the view that the bulk of aberrant promoter hypermethylation in cancer occurs predominantly at genes that are repressed in pre-cancerous tissue and therefore does not directly contribute to tumour progression by silencing tumour suppressor genes. This epigenetic alteration is common to all the cancer types, but does not result in a universal set of methylated genes, implying that a common mechanism is responsible for promoter hypermethylation at distinct sets of repressed genes in different cancers. Future research in this field should, therefore, focus on confirming whether aberrant hypermethylation does directly suppress rare ‘driver’ genes and if the mechanism responsible for driver gene suppression is the same or different to that acting at already repressed target genes.

This study contributes to the provocative question list raised by the National Cancer Institute ( Specifically question, PQB – 2; As we improve methods to identify epigenetic changes that occur during tumor development, can we develop approaches to discriminate between "driver" and "passenger" epigenetic events?

Author list: Duncan Sproul, Robert R Kitchen, Colm E Nestor, J Michael Dixon, Andrew H Sims, David J Harrison, Bernard H Ramsahoye and Richard R Meehan

Title : Tissue of origin determines cancer-associated CpG island promoter hypermethylation patterns

Journal: Genome Biology



Aberrant CpG island promoter DNA hypermethylation is frequently observed in cancer and is believed to contribute to tumor progression by silencing the expression of tumor suppressor genes. Previously, we observed that promoter hypermethylation in breast cancer reflects cell lineage rather than tumor progression and occurs at genes that are already repressed in a lineage-specific manner. To investigate the generality of our observation we analyzed the methylation profiles of 1,154 cancers from 7 different tissue types.


We find that 1,009 genes are prone to hypermethylation in these 7 types of cancer. Nearly half of these genes varied in their susceptibility to hypermethylation between different cancer types. We show that the expression status of hypermethylation prone genes in the originator tissue determines their propensity to become hypermethylated in cancer; specifically, genes that are normally repressed in a tissue are prone to hypermethylation in cancers derived from that tissue. We also show that the promoter regions of hypermethylation-prone genes are depleted of repetitive elements and that DNA sequence around the same promoters is evolutionarily conserved. We propose that these two characteristics reflect tissue-specific gene promoter architecture regulating the expression of these hypermethylation prone genes in normal tissues.


As aberrantly hypermethylated genes are already repressed in pre-cancerous tissue, we suggest that their hypermethylation does not directly contribute to cancer development via silencing. Instead aberrant hypermethylation reflects developmental history and the perturbation of epigenetic mechanisms maintaining these repressed promoters in a hypomethylated state in normal cells. 

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Unanticipated Consequences of DNA Hypomethylation; Loss and Gain of Polycomb Mediated Transcription Repression in Somatic Cells
By genome-wide mapping of the Polycomb Repressive Complex 2 (PRC2)-signature histone mark, H3K27me3, in DNA methylation-deficient mouse somatic cells, the Meehan lab shows that loss of DNA methylation is coincident with widespread H3K27me3 redistribution.
Monday, April 01, 2013
Non-Genotoxic Carcinogen Exposure Induces Defined Changes in the 5-Hydroxymethylome
In a genome wide study Meehan, Moggs and MARCAR co-authors examined 5mC and 5hmC profiles of liver in control and phenobarbital treated mice. They observe dynamic and reciprocal changes in the 5mC/5hmC patterns over genes promoters that are transcriptionally up-regulated.
Friday, October 05, 2012
Scientific News
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
World’s First Therapeutic Venom Database
Open-source library describes nearly 43,000 effects on the human body.
Mathematical Model Forecasts the Path of Breast Cancer
Chances of survival depend on which organs breast cancer tumors colonize first.
The Secret Behind the Power of Bacterial Sex
Migration between different communities of bacteria is the key to the type of gene transfer that can lead to the spread of traits such as antibiotic resistance, according to researchers at Oxford University.
Biomedical Imaging at One-Thousandth the Cost
Mathematical modeling enables $100 depth sensor to approximate the measurements of a $100,000 piece of lab equipment.
University of Glasgow Researchers Make An Impact in 60 Seconds
Early-career researchers were invited to submit an engaging, dynamic and compelling 60 second video illuminating an aspect of their research.
On Top of the Flu
Chance for advance warning in search-based tracking method.
TGAC Announces Milestone in Wheat Research
A more complete and accurate wheat genome assembly is being made available to researchers, by The Genome Analysis Centre (TGAC) on 12 November 2015.
Shedding Light on “Dark” Cellular Receptors
UNC and UCSF labs create a new research tool to find homes for two orphan cell-surface receptors, a crucial step toward finding better therapeutics and causes of drug side effects.
Is Allergy the Price We Pay for Our Immunity to Parasites?
New findings help demonstrate the evolutionary basis for allergy.
Scroll Up
Scroll Down

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos