Featured Research

from universities, journals, and other organizations

Breakthrough discovery unveils master switches in colon cancer

Date:
April 12, 2012
Source:
Case Western Reserve University
Summary:
Researchers have identified a new mechanism by which colon cancer develops. By focusing on segments of DNA located between genes, or so-called “junk DNA,” the team has discovered a set of master switches, i.e., gene enhancer elements, that turn “on and off” key genes whose altered expression is defining for colon cancers.

A team of researchers at Case Western Reserve University School of Medicine have identified a new mechanism by which colon cancer develops. By focusing on segments of DNA located between genes, or so-called "junk DNA," the team has discovered a set of master switches, i.e., gene enhancer elements, that turn "on and off" key genes whose altered expression is defining for colon cancers. They have coined the term Variant Enhancer Loci or "VELs," to describe these master switches.

Related Articles


Importantly, VELs are not mutations in the actual DNA sequence, but rather are changes in proteins that bind to DNA, a type of alteration known as "epigenetic" or "epimutations." This is a critical finding because such epimutations are potentially reversible.

Over the course of three years, the team mapped the locations of hundreds of thousands of gene enhancer elements in DNA from normal and cancerous colon tissues, pinpointing key target VELs that differed between the two types.

"What is particularly interesting is that VELs define a 'molecular signature' of colon cancer. Meaning, they are consistently found across multiple independent colon tumor samples, despite the fact that the tumors arose in different individuals and are at different stages of the disease," says Peter Scacheri, PhD, senior author of the study and assistant professor, Genetics and Genome Sciences, School of Medicine, and member, Case Comprehensive Cancer Center at Case Western Reserve University. "The set of common VELs govern a distinct set of genes that go awry in colon cancer."

"The VELs signature is notable because it cuts through the complexity of the many genes that are changed in colon cancer, to identify genes that are direct targets of alterations on chromosomes," says Sanford Markowitz, MD, PhD, Ingalls Professor of Cancer Genetics in the Division of Hematology-Oncology at the School of Medicine, member, Case Comprehensive Cancer Center, and oncologist at University Hospitals Seidman Cancer Center, whose team collaborated on the study. "The key next step will be to determine whether we can use VELs for 'personalized medicine,' to molecularly define distinct groups of colon cancers that differ in their clinical behavior, and to enable selection of specific drugs that will best treat a given colon tumor."

In addition to finding that VELs are a "signature" of colon cancer, the team showed that genetic variants which predispose individuals to colon cancer are located within VELs. This suggests that individual differences within VELs may play significant roles in determining different individuals' susceptibility to colon cancer.

"Epigenetics has transformed the way we think about genomes. The genetic code isn't just a series of As, Ts, Gs, and Cs strung together. Epigenetic 'marks' on DNA tell genes when, where, and how much to turn on or off to keep cells healthy," says Batool Akhtar-Zaidi, PhD candidate in Dr. Scacheri's lab and lead author of the study. "When this epigenetic machinery is disrupted, as we see with VEL events, this can tip the balance to cancer."

This research was supported by the National Cancer Institute, as well as the Case Comprehensive Cancer Center.


Story Source:

The above story is based on materials provided by Case Western Reserve University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Batool Akhtar-Zaidi, Richard Cowper-Sal·lari, Olivia Corradin, Alina Saiakhova, Cynthia F. Bartels, Dheepa Balasubramanian, Lois Myeroff, James Lutterbaugh, Awad Jarrar, Matthew F. Kalady, Joseph Willis, Jason H. Moore, Paul J. Tesar, Thomas Laframboise, Sanford Markowitz, Mathieu Lupien, Peter C. Scacheri. Epigenomic enhancer profiling defines a signature of colon cancer. Science, April 12, 2012 DOI: 10.1126/science.1217277

Cite This Page:

Case Western Reserve University. "Breakthrough discovery unveils master switches in colon cancer." ScienceDaily. ScienceDaily, 12 April 2012. <www.sciencedaily.com/releases/2012/04/120412141813.htm>.
Case Western Reserve University. (2012, April 12). Breakthrough discovery unveils master switches in colon cancer. ScienceDaily. Retrieved March 28, 2015 from www.sciencedaily.com/releases/2012/04/120412141813.htm
Case Western Reserve University. "Breakthrough discovery unveils master switches in colon cancer." ScienceDaily. www.sciencedaily.com/releases/2012/04/120412141813.htm (accessed March 28, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, March 28, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) — Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
Powered by NewsLook.com
These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) — A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. Video provided by Newsy
Powered by NewsLook.com
WH Plan to Fight Antibiotic-Resistant Germs

WH Plan to Fight Antibiotic-Resistant Germs

AP (Mar. 27, 2015) — The White House on Friday announced a five-year plan to fight the threat posed by antibiotic-resistant bacteria amid fears that once-treatable germs could become deadly. (March 27) Video provided by AP
Powered by NewsLook.com
House Ready to Pass Medicare Doc Bill

House Ready to Pass Medicare Doc Bill

AP (Mar. 26, 2015) — In rare bipartisan harmony, congressional leaders pushed a $214 billion bill permanently blocking physician Medicare cuts toward House passage Thursday, moving lawmakers closer to resolving a problem that has plagued them for years. (March 26) Video provided by AP
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:

More Coverage


Sifting Through 'junk' To Find Colorectal Cancer Clues

May 3, 2012 — Analysis of non-coding "junk" DNA has identified switches capable of turning on or off genes associated with the very common ... read more

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