Study shows epigenetic changes can drive cancer

July 25, 2014

Houston -- Cancer has long been thought to be primarily a genetic disease, but in recent decades scientists have come to believe that epigenetic changes - which don't change the DNA sequence but how it is 'read' - also play a role in cancer. In particular DNA methylation, the addition of a methyl group (or molecule), is an epigenetic switch that can stably turn off genes, suggesting the potential to cause cancer just as a genetic mutation can. Until now, however, direct evidence that DNA methylation drives cancer formation was lacking.

Researchers at the USDA/ARS Children's Nutrition Research Center at Baylor College of Medicine and Texas Children's Hospital have now created a mouse model providing the first in vivo evidence that epigenetic alterations alone can cause cancer. Their report appears today in the Journal of Clinical Investigation.

"We knew that epigenetic changes are associated with cancer, but didn't know whether these were a cause or consequence of cancer. Developing this new approach for 'epigenetic engineering' allowed us to test whether DNA methylation changes alone can drive cancer," said Dr. Lanlan Shen, associate professor of pediatrics at Baylor and senior author of the study.

Shen and colleagues focused on p16, a gene that normally functions to prevent cancer but is commonly methylated in a broad spectrum of human cancers. They devised an approach to engineer DNA methylation specifically to the mouse p16 regulatory region (promoter). As intended, the engineered p16 promoter acted as a 'methylation magnet'. As the mice reached adulthood, gradually increasing p16 methylation led to a higher incidence of spontaneous cancers, and reduced survival.

"This is not only the first in vivo evidence that epigenetic alteration alone can cause cancer," said Shen. "This also has profound implications for future studies, because epigenetic changes are potentially reversible. Our findings therefore both provide hope for new epigenetic therapies and validate a novel approach for testing them."

Shen, who is also with the NCI-designated Dan L. Duncan Cancer Center at Baylor, predicts that this new approach will be widely useful because in addition to p16, there are many other genes and diseases other than cancer that are connected to epigenetics (such as neurodevelopmental diseases, obesity and diabetes). Just as genetic engineering has become a standard approach for studying how genetic mutations cause disease, epigenetic engineering will now enable functional studies of epigenetics.

"This opens up the door for a whole new paradigm of how to understand tumorigenesis. If we can identify epigenetic changes that predispose people to cancer, these may actually be treatable or preventable, so this opens up a lot of optimism in new ways to deal with cancer," said Dr. Robert Waterland, associate professor of pediatrics at Baylor, who was also involved in the study.
-end-
Others who took part in the study include Da-Hai Yu, Pumin Zhang, Deborah Schady, Miao-Hsueh Chen, Yongtao Guan and Manasi Gadkari, all with Baylor.

Funding for this study came from grants from the Sidney Kimmel Foundation, the U.S. Department of Agriculture, the March of Dimes and the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK081557), a part of the National Institutes of Health.

Baylor College of Medicine

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.