Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

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 (http://provocativequestions.nci.nih.gov/rfa). 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


 
Summary

Background

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.

Results

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.

Conclusions

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

Join For Free

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 3,000+ scientific posters on ePosters
  • More than 4,400+ 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 TechnologyNetworks.com 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
Cell Transplant Treats Parkinson’s in Mice
A University of Wisconsin—Madison neuroscientist has inserted a genetic switch into nerve cells so a patient can alter their activity by taking designer drugs that would not affect any other cell.
Skin Cells Turned into Heart Cells and Brain Cells Using Drugs
In a scientific first, Gladstone researchers have used chemical drugs to convert skin cells into heart cells and brain cells, without adding any external genes.
Shape Of Tumor May Affect Whether Cells Can Metastasize
Illinois researchers found that the shape of a tumor may play a role in how cancer cells become primed to spread.
‘Mini-Brains’ to Study Zika
Novel tool expected to speed research on brain and drug development.
Cytokine Triggers Immune Response at Expense of Blood Renewal
Research highlights promise of Anti-IL-1 drugs to treat chronic inflammatory disease.
AstraZeneca to Sequence 2 Million Genomes in Search for New Drugs
Company launches integrated genomics approach which aims to transform drug discovery and development.
Improving Engineered T-Cell Cancer Treatment
Purdue University researchers may have figured out a way to call off a cancer cell assassin that sometimes goes rogue and assign it a larger tumor-specific "hit list."
Micro Heart Muscle Created from Stem Cells
Researchers have designed a new way to create micro heart muscle from stem cells using a unique dog bone dish.
Immune Booster Tested in Advanced Merkel Cell Cancer
The immunotherapy drug produced durable responses in many patients.
Mutated Mitochondria Found in Stem Cells
Researchers find hidden genetic mutations in patient-derived stem cells which could ultimately undermine therapeutic benefit.
SELECTBIO

SELECTBIO Market Reports
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
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,400+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!