We’ve heard that DNA methylation can get messed up in cancer, but what about 5-hydroxymethylation (5-hmC)? In a recent report, researchers say that 5-hmC profiles could serve as epigenetic signatures of cancer.
The U.K. and Swiss team wanted to know if they could zero in on a signature or biomarker for liver cancer—specifically for liver cancer that develops from exposure to a non-genotoxic carcinogen (one that doesn’t directly mess with DNA). A typical way to study this in rodents is with phenobarbital (PB).
They looked at normal livers and those from mice exposed to PB. Here’s some of what they found:
- 5-hmC patterns are conserved between normal mice of the same age. But 5-methylcytosine (5-mC) patterns weren’t as conserved.
- Global 5-hmC patterns change during maturation, and you can even use those patterns to figure out how old a liver is—but that doesn’t really work with 5-mC patterns, though.
- Short-term PB doses caused reproducible 5-hmC changes, but 5-mC changes were variable. Global 5-mC changes got more reproducible with longer-term PB exposure.
- Changes in both modifications increased with longer PB exposure, with the hydroxymethylome changing more than the methylome. The modifications also got redistributed.
- They identified several genes that could serve as biomarkers for PB-driven cancers.
“Drug exposure generates a unique epigenetic barcode (“EPICODE”) of chemical exposure, which may aid in better understanding of disease and cancer progression,” says Richard Meehan of the MRC Human Genetics Unit, University of Edinburgh and Western General Hospital. “5-hydroxymethylcytosine profiling has the potential to become a standard diagnostic tool in personalized medicine.”
Read more about the study at Nucleic Acids Research, April 2013.