Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
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 2,700+ scientific posters on ePosters
  • More than 3,800+ 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
Coupling Genome Defence to Epigenetic Reprogramming
The work, just published in Development, identifies genes DIRECTLY regulated by DNA methylation.
Thursday, September 06, 2012
Scientific News
Biomarker Predicting Transplant Complications May be Key to Treating Them
A protein that can be used to predict if a stem cell transplant patient will suffer severe complications may also be the key to preventing those complications, an international research team based at the Indiana University School of Medicine reported Wednesday.
Snapshot Turns T Cell Immunology on its Head
New research may have implications for 1 diabetes sufferers.
Developing a Gel that Mimics Human Breast for Cancer Research
Scientists at the Universities of Manchester and Nottingham have been funded to develop a gel that will match many of the biological structures of human breast tissue, to advance cancer research and reduce animal testing.
Lung Repair and Regeneration Gene Discovered
New role for hedgehog gene offers better understanding of lung disease.
Restoring Vision with Stem Cells
Age-related macular degeneration (AMRD) could be treated by transplanting photoreceptors produced by the directed differentiation of stem cells, thanks to findings published today by Professor Gilbert Bernier of the University of Montreal and its affiliated Maisonneuve-Rosemont Hospital.
The Age of Humans Controlling Microbes
Engineered bacteria could soon be used to detect environmental toxins, treat diseases, and sustainably produce chemicals and fuels.
Gene Expression: A Snapshot of Stem Cell Development
New genes found that regulate development of stem cells.
Tissue-Engineered Colon from Human Cells
A study by scientists at Children’s Hospital Los Angeles has shown that tissue-engineered colon derived from human cells is able to develop the many specialized nerves required for function, mimicking the neuronal population found in native colon.
Tension Helps Heart Cells Develop Normally in the Lab
Stanford engineers have uncovered the important role tension plays in growing heart cells out of the body.
Urine Excretion From Stem Cell-Derived Kidneys
Researchers report a strategy for enabling urine excretion from kidneys grown from stem cells.
Skyscraper Banner

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
2,700+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos