The evolution of an aggressive tumour

Australia’s iconic Tasmanian Devil (Sarcophilus harrisii) is particularly prone to a cancer that spreads through biting, causes large welts on the marsupial’s face, and eventually leads to death. 

Devil Facial Tumour 1 (DFT1), as it is known, was first seen in 1996, but scientists have not really understood how it became so aggressive and infectious in just a couple of decades.

Now a study by researchers in the UK and Australia, led by Young Mi Kwon from the University of Cambridge, has thrown new light on DFT1’s evolutionary dynamics, and may have broader implications for our understanding of cancers in humans.

Their work, described in a paper in the journal PLOS Science, found that the DFT1 genomes is highly stable, has changed little over time, and has specifically adapted to overcome the devil’s immune response. And unlike in human tumours, there is not a lot of genetic variation.

This shows, the researchers write in their paper, “how a comparatively simple and stable cancer cell lineage can colonise diverse niches and devastate a species”. 

Once found all over Australia, S. harrisii, the world’s largest carnivorous marsupial, is now only in the island state of Tasmania. For this study, Kwon and his team analysed 648 DFT1 genomes collected around the state between 2003 and 2018. 

They found that DFT1 very quickly diverged into five separate groups, or clades, but a couple of these died out.  More recently, one clade appears to have mostly taken over in many locations. The researchers were even able to track this flow to see how the devils were moving around and spreading infection to each other across different parts of Tasmania.

“The spatial and temporal dynamics of DFT1 between 2003 and 2018, described here, reveal not only the trajectories of parallel and competing DFT1 sublineages but also trace the patterns of movement of the diseased devils themselves,” they write in their paper.

This may have been exacerbated when humans removed diseased devils from the population. That may have prevented some strains spreading, but it also meant another clade had the chance to take over when a wandering devil picked a fight.

Regardless, they also found that infected devils could still catch another strain of DFT1. This means being infected by DFT1 does not necessarily inoculate the devil against other strains, so a vaccine is unlikely to be effective.

Despite this, DFT1 appeared to have a stable genome, unlike human cancers that generally have lots of genetic variation. Interestingly, though, this was not because the genome didn’t experience mutation, but rather because genes that were lost during evolution were regained later because they helped DFT1 survive. 

In particular, some of these genes may have lowered the devil’s immune response. Cancers that don’t trigger an immune response are much more likely to establish themselves and become aggressive when one devil bites another.

To investigate how these cancers adapt, the team also grew DFT1 cells in the lab. They started with 24 different lines, but observed that, over time, the genomes experienced convergent evolution. This is a phenomenon where genomes or physical traits become more similar, instead of diverging. 

“Although positive selection continues to mould the DFT1 genome, most genetic alterations in DFT1 are unlikely to offer an advantage. Indeed, the gradual accumulation of mutations may, in the long term, reduce the lineage’s robustness, especially given evidence that negative selection may be inefficient in transmissible cancers,” the researchers write.

Ultimately, this means the aggressive nature of DFT1 might not be due to lots of extra mutations, as with human tumours, but because it remains genetically stable. This information can be used to predict how DFT1 will evolve in the future and emphasises the highly complex evolution of cancers in all species, including humans.