Around 11,000 years ago, a dog became immortal. One of its cells started growing and dividing uncontrollably, giving rise to a tumour. And one of the cells from that tumour became contagious. It gained the ability to leave its original host and infect new ones. It jumped into another dog, and another, and another, creating a fresh tumour in each new host. That original dog is long dead, but in a way, it lives on in the contagious cancer that it spawned.
That cancer, now known as canine transmissible venereal tumour (CTVT), has since travelled across six continents, spreading from dog to dog by sex or close contact. It’s a global parasite. It’s also the oldest living cancer.
A Russian veterinarian named Mstislav Novinski first described this contagious cancer in the 1870s, but it took till 2006 for Robin Weiss and Claudio Murgia from University College London to discover its true nature. By comparing tumour samples from 40 dogs across the world, the team showed that CTVT tumours are more closely related to each other than to cells from their host dogs. In other words, they hadn’t arisen independently in each host. They were all descendants of that same original contagious cancer.
And this cancer hasn’t gone unchanged during its travels. On occasion, it has swapped out its batteries.
Our cells are powered by tiny bean-shaped structures called mitochondria. These are passed down from mother to daughter, and they have their own small independent genomes. This should mean that all the mitochondria in every CTVT cell descends from that ancestral tumour, and that it should be possible to map their genomes only to a single exclusive family tree.
It’s not. In 2011, Clare Rebbeck analysed mitochondrial genomes from 37 tumour samples and found that they belonged to two main lineages, each of which clustered with a different group of dogs. This strongly suggested that the contagious cancers occasionally pick up new mitochondria from their hosts.
How many times has this happened? At least five, according to Andrea Strakova and Máire Ní Leathlobhair from the University of Cambridge. They got that number through the biggest survey yet of CTVT—a whopping 449 tumours from 39 countries. They showed that the mitochondria of these tumours group into five different lineages, implying five replacement events.
All of these lineages are younger than 1,700 years, and CTVT itself is at least 11,000 years old. This means that the original mitochondria from the founder dog that first spawned these tumours are no more. They were replaced.
No one knows how these mitochondrial swaps occur. Tumour cells might grab the mitochondria of new hosts by fusing with their cells. Alternatively, “it’s possible that little tubules form between the tumour and host cells,” says Elizabeth Murchison, who led the new study. Mitochondria then travel along these bridges.
It’s also unclear why this happened. “That it happened five times suggests that it conferred some kind of advantage,” says Murchison. Mitochondria burn a lot of energy and their DNA has a habit of changing quickly. Many of these changes will be harmful. But as the CTVT cells go on the move, they can swap their worn-out batteries with fresh ones from new hosts.
Supporting this idea, Murchison’s team found an unusually low number of disruptive mutations among their mitochondrial genomes. “In cancer, that’s not usually the case; cancer cells aren’t very good at protecting essential genes,” she says. “This suggests that the mitochondrial DNA is probably quite important for the viability of CTVT.”
There are also four other transmissible tumours: two that affect Tasmanian devils, one in shellfish, and another in captive Syrian hamsters. Studying these unusual cancers, Murchison says, gives us clues about the biology of normal ones that don’t spread between hosts.
For example, the team found signs that the mitochondria of CTVT cells can sometimes shuffle their DNA with the mitochondria of their hosts. This is called recombination, and it has never been seen in cancer cells before. This could be happening in human cancers and we’d never know because the mixing mitochondria would have nigh-identical genomes. But if it did happen, “it may be important for maintaining and repairing mitochondrial DNA,” Murchison says. “
Contagious cancers can also be informative in unexpected ways. For example, the history of the five contagious cancer lineages reveals the history of dogs, which in turn reveals the history of humans. One lineage is widespread throughout Eurasia, but only reached the Americas around 500 years ago, reflecting Europe’s colonisation of the New World. Another lineage seems to have spread through trade routes across the Atlantic and Indian oceans. As humans criss-crossed the world, we took our dogs with us—and their contagious tumours followed.
It is sobering to think that this rogue cancer—this immortal dog—will likely outlive you, me, and everyone who currently studies it.