The Tasmanian devil, Sarcophilus harrisii, faces extinction within the next 25 years because of a clonally transmissible cancer called devil facial tumor disease (DFTD). The deadly parasitic cancer is transmitted between the Australian marsupials by cell implantation that occurs during biting each other in their social interactions. Since the disease emerged 15 years ago, the population has decreased by about 70%.
In a paper published in Proceeding of the Royal Society, researchers from the University of Sydney described the epigenetic changes and underlying mechanisms in cells infected with DFTD.
“Nobody has looked at the role of epigenetics in this devastating disease,” said Beata Ujvari, post-doctoral research fellow at the University of Sydney. “And although the tumor or this cancer cell line appears to be stable on the genomic, genetic, and stereotypic levels, it’s actually quite polymorphic on the epigenomic level which we were quite surprised by.”
Changes on the epigenetic level can affect whether a gene is expressed or not through external or environmental factors without altering DNA sequence. The results show that the epigenetic markers in devil tumor cells are actually removed over time, turning the expression of certain genes off. Because DFTD is passed from animal to animal, it is exposed to many different environments. This allows selection to act on different tumor variants to push the cancer’s evolution forward.
To understand the potential epigenetic changes in DFTD cells, the researchers measured the tumor cells’ DNA methylation, which drives epigenetic processes and is essential for the regulation of gene expression and genomic stability.
To do this, the team measured genetic and epigenetic variations between tumor and other tissue samples collected over a six-year span using two molecular techniques: amplified fragment length polymorphism (AFLP) to detect genetic variation and methylation-specific AFLP (metAFLP) to detect methylation variation.
Using these techniques, the group found that while the tumor samples were identical on the genetic level, they were highly variable and polymorphic on the epigenetic level. In addition, the researchers found that methylation loss was due to a significant increase in hypomethylation, which can actively silence tumor-suppressor genes over time.
Ujvari believes that by understanding how cancer evolves in DFTD, researchers may have a better way to begin studying cancer evolution functions in humans. “No human cancer studies so far have attempted to follow or study the effect of epigenetic changes over time,“ said Ujvari.
But for now, Ujvari and her colleagues would like to find and target the regions or exact genes that are involved in actively losing methylation in order to find potential answers to the problem.
“Unfortunately the technique metAFLP did not allow us to specify the exact gene regions which were differentially methylated over time; therefore we aim to use bisulfite sequencing of tumour samples to identify the regions/genes with different methylation patterns,” explained Ujvari.
1. Ujvari, B., A.-M. Pearse, S. Peck, C. Harmsen, R. Taylor, S. Pyecroft, T. Madsen, A. T. Papenfuss, and K. Belov. 2012. Evolution of a contagious cancer: epigenetic variation in devil facial tumour disease.Proceedings of the Royal Society B: Biological Sciences (November).