A recent study offers the first in vivo evidence that epigenetic alterations alone can cause cancer.As known to us, epigenetic alterations don’t change the DNA sequence but how it expresses. In particular, DNA methylation as an epigenetic switch stably turn off genes, suggesting the potential to cause cancer just as a genetic mutation can.

Direct evidence that DNA methylation drives cancer formation was lacking for a long while. Researchers at Baylor College of Medicine and Texas Children’s Hospital have currently created a mouse model, allowing to validate the effect of DNA methylation on cancer.

Investigators 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, but also has profound implications for future studies, because epigenetic changes are potentially reversible. The findings therefore provide hope for new epigenetic therapies and validate a novel approach for testing them.”

A researcher 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 diabetes).As another researcher say, “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”.

Reference:Targeted p16Ink4a epimutation causes tumorigenesis and reduces survival in mice. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI76507