Epigenetics is being associated with numerous health conditions and diseases including cancer. It is defined as changes in gene expression caused by the environment. The most common form of epigenetics consists of methylation, the addition of an methyl group (or molecule) ncer has long been thought to be primarily a genetic disease, but in recent decades scientists have come to believe which acts as a switch to turn cancer on and off.
Researchers at the USDA/ARS Children’s Nutrition Research Center at Baylor College of Medicine and Texas Children’s Hospital have tested the cancer epigenetic theory in a mouse model providing the first in vivo evidence that epigenetic alterations alone can cause cancer. A methylated version of the p16 gene was associated with a wide variety of human cancers. The mouse model tested the association of the p16 gene with cancer by genetically engineering the p16 promoter which acted as a methylation magnet. As the mice reached adulthood, increased p16 methylation led to a higher incidence of spontaneous cancers, and reduced survival.
“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.
“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.”
“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.
Da-Hai Yu, Robert A. Waterland, Pumin Zhang, Deborah Schady, Miao-Hsueh Chen, Yongtao Guan, Manasi Gadkari, Lanlan Shen. Targeted p16Ink4a epimutation causes tumorigenesis and reduces survival in mice. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI76507