Epigenomic abnormalities predict patient survival in non-Hodgkins lymphoma

January 10, 2013

Think of the epigenome like a giant musical mixing board, turning up or down the expression of various genes. A University of Colorado Cancer Center study published today in the journal PLOS Genetics shows that in cancer, not only can genes themselves go bad, but abnormal changes in the epigenetic mixing board can unfortunately change the expression of these genes. Researchers hope to play the role of sound engineers, controlling these harmful epigenomic changes to turn down cancer itself or perhaps sensitize cancers to existing drugs.

The epigenome's primary tool – and by far the easiest to study – is methylation: it attaches little to near the genes to silence or promote their expression.

"Not only do we see more abnormal methylation in non-Hodgkin than in healthy B-, but there are three distinct subtypes of the disease in the clinic, each more aggressive than the next. These three clinical of non-Hodgkins lymphoma were distinctly marked by their levels of abnormal methylation," says Subhajyoti De, PhD, CU Cancer Center investigator and assistant professor at the CU School of Medicine.

In other words, methylation patterns predict patient survival. Here's how it works:

DNA should be methylated in a consistent way – you get a certain, standardized amount of methyl "residue" attached to your genes. Sure enough, that's the case in healthy B-cells. Subhajyoti and colleagues show that in cancerous B-cells, the level of from cell to cell varies wildly. And the more wildly the level of DNA methylation varies, the more aggressive is the cancer. It's as if, in the body, you want a consistent epigenome that maintains the methylation of the healthy status quo –when a willy-nilly epigenome drops methylation randomly here and there, it promotes non-normal cells, like cancer.

So abnormal methylation is certainly correlated with not only cancer, but with the aggressive behaviors of cancer subtypes. But what exactly is the functional role of this methylation?

"We think that in addition to genetic mutations that cause cancer, epigenetic changes probably play a subtle role that allows the cancer to thrive within our body," Subhajyoti says.

There are drugs that affect the epigenome's ability to methylate and so control genes – some of which crescendo or decrescendo the amount of methylation across the board, and some of which affect the amount of methylation on certain genetic products. Does one of these drugs hold the key to muting cancer?

Subhajyoti hopes to find out.

"For the last 50 years, the scientific community pushed to identify the genetic drivers of cancer, but now in the past five or six years we've expanded the search into the epigenome as well," Subhajyoti says. "We now expect to find that both genetic and epigenetic abnormalities are important for initiation and maintenance of cancer."

Explore further: New insights into why humans are more susceptible to cancer and other diseases

Related Stories

New insights into why humans are more susceptible to cancer and other diseases

August 23, 2012
Chimpanzees rarely get cancer, or a variety of other diseases that commonly arise in humans, but their genomic DNA sequence is nearly identical to ours. So, what's their secret? Researchers reporting in the September issue ...

Researchers complete the first epigenome in Europe

May 30, 2012
A study led by Manel Esteller, director of the Epigenetics and Cancer Biology Program at the Bellvitge Biomedical Research Institute (IDIBELL), professor of genetics at the University of Barcelona and ICREA researcher, has ...

Researchers discover biomarkers for prostate cancer detection, recurrence

May 14, 2012
Alterations to the "on-off" switches of genes occur early in the development of prostate cancer and could be used as biomarkers to detect the disease months or even years earlier than current approaches, a Mayo Clinic study ...

Study discovers genetic pathway impacting the spread of cancer cells

May 3, 2012
In a new study from Lawson Health Research Institute, Dr. Joseph Torchia has identified a new genetic pathway influencing the spread of cancer cells. The discovery of this mechanism could lead to new avenues for treatment.

Cancer cells' universal 'dark matter' exposed

June 26, 2011
Using the latest gene sequencing tools to examine so-called epigenetic influences on the DNA makeup of colon cancer, a Johns Hopkins team says its results suggest cancer treatment might eventually be more tolerable and successful ...

Recommended for you

New approach to studying chromosomes' centers may reveal link to Down syndrome and more

November 20, 2017
Some scientists call it the "final frontier" of our DNA—even though it lies at the center of every X-shaped chromosome in nearly every one of our cells.

Genome editing enhances T-cells for cancer immunotherapy

November 20, 2017
Researchers at Cardiff University have found a way to boost the cancer-destroying ability of the immune system's T-cells, offering new hope in the fight against a wide range of cancers.

A math concept from the engineering world points to a way of making massive transcriptome studies more efficient

November 17, 2017
To most people, data compression refers to shrinking existing data—say from a song or picture's raw digital recording—by removing some data, but not so much as to render it unrecognizable (think MP3 or JPEG files). Now, ...

Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)

November 15, 2017
The first genetic mutation that appears to protect against multiple aspects of biological aging in humans has been discovered in an extended family of Old Order Amish living in the vicinity of Berne, Indiana, report Northwestern ...

US scientists try first gene editing in the body

November 15, 2017
Scientists for the first time have tried editing a gene inside the body in a bold attempt to permanently change a person's DNA to try to cure a disease.

Genetic variant prompts cells to store fat, fueling obesity

November 13, 2017
Obesity is often attributed to a simple equation: People are eating too much and exercising too little. But evidence is growing that at least some of the weight gain that plagues modern humans is predetermined. New research ...

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.