Breakthrough study finds 'master switches' in colon cancer

April 12, 2012

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.

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 , 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 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 ."

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 .

"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."

Explore further: Study shows how high-fat diets increase colon cancer risk

More information: "Epigenomic enhancer profiling defines a signature of colon cancer" is published advanced online in Science Express.

Related Stories

Study shows how high-fat diets increase colon cancer risk

March 7, 2012
Epidemiologists have long warned that, in addition to causing obesity, eating too much fat and sugar puts a person at greater risk for colon cancer. Now, researchers at Temple University have established a link that may explain ...

New clinical trial explores novel noninvasive colon cancer screening test

April 2, 2012
In a first-of-its-kind clinical trial, physician-scientists at University Hospitals (UH) Case Medical Center's Seidman Cancer Center and Case Western Reserve University School of Medicine are studying a promising new non-invasive ...

Recommended for you

An architect gene is involved in the assimilation of breast milk

October 17, 2017
A family of "architect" genes called Hox coordinates the formation of organs and limbs during embryonic life. Geneticists from the University of Geneva (UNIGE) and the Swiss Federal Institute of Technology in Lausanne (EPFL), ...

Study identifies genes responsible for diversity of human skin colors

October 12, 2017
Human populations feature a broad palette of skin tones. But until now, few genes have been shown to contribute to normal variation in skin color, and these had primarily been discovered through studies of European populations.

Genes critical for hearing identified

October 12, 2017
Fifty-two previously unidentified genes that are critical for hearing have been found by testing over 3,000 mouse genes. The newly discovered genes will provide insights into the causes of hearing loss in humans, say scientists ...

Team completes atlas of human DNA differences that influence gene expression

October 11, 2017
Researchers funded by the National Institutes of Health (NIH) have completed a detailed atlas documenting the stretches of human DNA that influence gene expression - a key way in which a person's genome gives rise to an observable ...

Genetic advance for male birth control

October 10, 2017
When it comes to birth control, many males turn to two options: condoms or vasectomies. While the two choices are effective, both methods merely focus on blocking the transportation of sperm.

Researchers uncover new congenital heart disease genes

October 9, 2017
Approximately one in every 100 babies is born with congenital heart disease (CHD), and CHD remains the leading cause of mortality from birth defects. Although advancements in surgery and care have improved rates of survival ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.