Featured Research

from universities, journals, and other organizations

Prostate cancer risk variant found to be in a functional DNA sequence linked with disease

Date:
July 19, 2010
Source:
Cold Spring Harbor Laboratory
Summary:
Recent genetic association studies have uncovered a number of DNA variants associated with prostate cancer. However, some of these risk variants lie outside of genes, posing a challenge to researchers working to understand the biology of cancer. In a new study, researchers have characterized a functional DNA element associated with prostate cancer, lending new insight into the molecular mechanisms of the disease.

Recent genetic association studies have uncovered a number of DNA variants associated with prostate cancer. However, some of these risk variants lie outside of genes, posing a challenge to researchers working to understand the biology of cancer. In a report published online in Genome Research, researchers have characterized a functional DNA element associated with prostate cancer, lending new insight into the molecular mechanisms of the disease.

Related Articles


Genome wide association studies (GWAS) have uncovered numerous genetic variants that confer increased risk to disease, and interestingly, many reside in genomic regions that lack genes. Although the DNA may not code for a gene, it could still play a functional role. "This raises the question of what non-coding DNA within these gene deserts actually has biological function, and how differences within a functional non-coding element could underlie disease risk," said Marcelo Nobrega of the University of Chicago, senior author of the study.

Recent GWAS have implicated a specific region of chromosome 8, known as 8q24, for harboring non-coding risk variants for several different cancers, including particularly strong associations with prostate cancer. Variants in this region could lie within enhancer elements, non-coding DNA sequences that control how, when, and where genes are expressed. An altered enhancer sequence could significantly change the normal expression of critical genes, increasing risk for disease.

To test this hypothesis, the group designed an experiment to investigate the enhancer activity of human 8q24 DNA fragments and whether risk alleles of the enhancer modify that activity. The group engineered DNA segments that included the human sequences and a "reporter" gene that would indicate whether any enhancers are present in the human DNA.

They then created transgenic mice that harbored the engineered DNA sequences in every cell of the animal. If a human enhancer interacts with the reporter gene in any tissue, the cells turn blue when treated with a stain.

"By looking at the transgenic mice we noticed that their prostate and mammary glands were blue," Nobrega noted, "indicating the presence of regulatory sequences within the piece of human DNA that we were testing." They then focused on the prostate, identifying the specific enhancer driving the observed expression pattern.

The group could then engineer a version of the enhancer that contained a risk variant associated with prostate cancer and test this in mice. The prostate enhancer harboring the risk allele in the sequence drove expression of the reporter gene significantly higher in the mouse prostate relative to the normal version of the enhancer.

"The fact that a single nucleotide difference so markedly altered the enhancer's activity within the context of a living organism clearly demonstrates the potential impact that variation within non-coding gene regulatory elements could have on disease state," Nobrega noted.

Previous research has indicated that this enhancer modifies activity of a nearby gene called MYC, a proto-oncogene that exhibits altered expression in prostate cancers. However, those studies found no correlation between the risk allele enhancer and MYC expression in normal or cancerous prostate tissues, suggesting altered MYC expression may not be the biological factor conferring risk to disease in these cases.

The authors further explained that the risk variant enhancer activity was observed in the prostate throughout organogenesis and development, suggesting that the cancer risk variant might assert its influence very early, long before a tumor forms. "This strengthens the notion of a pathogenic process that could initiate much earlier in life than the appearance of clinical alterations, one in which this prostate enhancer could potentially play a part," said Nora Wasserman, primary author of the study.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Wasserman NF, Aneas I, Nobrega MA. An 8q24 gene desert variant associated with prostate cancer risk confers differential in vivo activity to a MYC enhancer. Genome Research, 2010; DOI: 10.1101/gr.105361.110

Cite This Page:

Cold Spring Harbor Laboratory. "Prostate cancer risk variant found to be in a functional DNA sequence linked with disease." ScienceDaily. ScienceDaily, 19 July 2010. <www.sciencedaily.com/releases/2010/07/100712171703.htm>.
Cold Spring Harbor Laboratory. (2010, July 19). Prostate cancer risk variant found to be in a functional DNA sequence linked with disease. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2010/07/100712171703.htm
Cold Spring Harbor Laboratory. "Prostate cancer risk variant found to be in a functional DNA sequence linked with disease." ScienceDaily. www.sciencedaily.com/releases/2010/07/100712171703.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com
Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins