Andrea Strakova & Máire Ní Leathlobhair, The University of Cambridge
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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, which emerged in one single dog 11,000 years ago, the cells from that animal’s cancer are infectious and they can spread to other dogs, causing genital and facial tumours, 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 researchers Andrea Strakova and Máire Ní Leathlobhair at the department of veterinary medicine...
Andrea - We looked at CTVT tumours from different parts of the world. So 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. They have a small piece of DNA which codes for the proteins needed by the mitochondria. We looked at the mutations or genetic changes in this mitochondrial DNA which gave us a unique opportunity to look at the ways that the disease spread 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 contract it 11,000 years ago. Meaning, it can be traced back to that time. But very occasionally throughout history, a tumour in a specific dog has done something a little unusual and grabbed mitochondrial DNA from cells of the host dog.
Máire - My name is Máire Ní Leathlobhair and I'm a second year PhD student in the Transmissible Cancer group. We were able to use the kind of phenomenon of horizontal transfer in CTVT cells as a kind of cellular tracking device. If you can imagine that usually, dogs would carry around their own normal mitochondria but these host mitochondria then swapped into the cancer cells and these were spread throughout global dog populations over hundreds to thousands of years. Using these and kind of the patterns we saw across our global population of samples, we’re able to track how different groups of dogs afflicted with CTVT 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 throughout time. 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 - So, from the five different transfers of mitochondria, we were able to define five different clades. The timing of these clades was based on the mutations which we found in each of the mitochondria.
Georgia - By working out the just 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 used a so-called molecular clock so we can look at the number of mutations which we see in each of these different mitochondrial types. 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 described.
Georgia - Why would this happen?
Andrea - Well, we think one of the reasons could be that the mitochondria in the tumour have so many mutations that they would be in a way less functional. And therefore, gaining mitochondria from the normal dog, that would provide a selective advantage for the cell.
Georgia - By grabbing this mitochondrial DNA from healthy dogs, they can reduce the number of harmful genetic changes that will have built up over time – a very clever trick. But the team came across something even more surprising.
Andrea - Well, we found one very, very special case in a dog in Nicaragua. What actually happened in this dog is that not only that the mitochondria jumped 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 - 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 that 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, they would be a potential for targeted treatment.