Andrea Strakova & Máire Ní Leathlobhair, The University of Cambridge
CTVT, or canine transmissible venereal tumour, is very unusual kind of cancer. The majority of cancers we see arise from an individual’s own cells, but in this dog tumour the cells from that animal’s cancer are infectious and they can spread to other dogs when the animals mate. Now scientists at Cambridge University have studied dogs with the cancer from around the world, turning up a big surprise: the cancers have adopted DNA from the host dogs they’ve infected. Specifically this has happened in structures inside cells called mitochondria, which provide cells with their energy and this is how the tumour keeps fit. Georgia Mills went to see researcher Andrea Strakova at the department of veterinary medicine...
Andrea - We collected over 400 samples from 39 countries around the world and we looked at the mitochondrial DNA of these samples. So mitochondria are, let's say, batteries of the cell, which provide energy and they have a small piece of DNA which codes for the proteins needed by the mitochondria. And we looked at the mutations, or genetic changes in these mitochondrial DNA, which gave us a unique opportunity to look at the ways that the disease spreads around the world.
Georgia - Because these cancer cells are transferred directly from dog to dog, cells in each tumour are from the original dog to contracted it 11,000 years ago, meaning it can be traced back to that time. But, very occasionally throughout history, the tumour in a specific dog has done something a little usual and grabbed mitochondrial DNA from cells of the host dog.
Mora - My name is Máire Ní Leathlobhair and I’m a second year PhD student in the transmissible cancer group. If you can imagine that dogs usually carry around their own normal mitochondria, but these host mitochondria then swapped into the cancer cells and then these are spread throughout global dog populations over hundreds to thousands of years. And using these patterns we saw across global population of samples we were able to track how different groups of dogs afflicted with CTV moved.
Georgia - This snatching of DNA happened at least five times in history, meaning the team could get a clearer idea of the movement of infected dogs through time, and this pattern matched old trade routes across the ocean so it looks like people took their dogs with them to the high seas. Andrea…
Andrea - From the five different transfers of mitochondria, we were able to define five different clades, and the timing of the clades was based on the mutations we found in each of the mitochondria.
Georgia - By working out the normal background rate of mutations, you can look at these, you can take the DNA from the dogs that are infected, look at the DNA in the mitochondria and then find out how old this cancer is?
Andrea - Exactly, because we use the so called molecular clock. So we can look at the number of mutations, which we see in each of these different mitochondrial types, and that helps us to look at the timing when each of them arise.
Georgia - And then these different clades are from when these big events when mitochondrial DNA switched?
Andrea - Exactly. So these are from the time when the mitochondrial DNA from the dog actually jumped into the tumour cell, and this was the switch as you describe.
Georgia - Why would this happen?
Andrea - Well, we think that one of the reasons could be that the mitochondria in the tumour has so many mutations that they would be, in a way, less functional and therefore, gaining the mitochondria from the normal dog, that would provide a selective advantage for the cell.
Georgia - By grabbing this mitochondrial DNA from the healthy dogs they can reduce the amount of harmful genetic changes that will have built up over time. A very clever trick, but the team came across something even more surprising…
Andra - Well, we found one very, very, special case in a dog in Nicaragua. What actually happened in this dog is that not only did the mitochondria jump from the dog into the tumour cell but actually, we found that these two mitochondria mixed to create a single mitochondria, formed both by the tumour and the dog DNA.
Georgia - And why is this unusual?
Andrea - This is something that has never been reported in cancers before. We believe this could be because it may be very difficult to detect so we suspect this process could actually be a lot more common than expected, but we just don’t have the tools to detect it. So what we are planning to do in the future is to look more widely to see if this type of mitochondrial mixing is found in other tumours around the world. And also, it would be very interesting to see if we can see this type of mixing in human cancers as well.
Georgia - Do you think this would have any implications for cancer treatment?
Andrea - If mitochondrial recombination is, indeed, common in human cancers as well, then certainly there would be a potential for targeted treatment.