The world’s oldest cancer may also be the world's weirdest. A new natural history of a sexually-transmitted dog cancer reveals the evolutionary twists and turns that have kept the disease going for thousands of years. The report was published in the journal eLife.
As a contagious cancer, the disease known as canine transmissible venereal tumor (CTVT) was already pretty unique. Researchers are aware of only four types of transmissible cancer, none of which can be contracted by humans. One type passes between Tasmanian devils through a bite on the face. Another washes through ocean water from clam to clam. The third type is transmitted through mosquito bites to Syrian hamsters. The last, oldest, and most widespread, is CTVT.
Studies suggest that the very first dog to develop CTVT lived around 11,000 years ago. Dog Zero died, but its cancer lived on in a second dog, and then a third, on and on. Today the disease has affected dogs in at least 90 countries, and it continues to spread.
To find out what makes this particular form of cancer so resilient, an international team of researchers examined DNA in the mitochondria of tumor samples from 449 dogs in 39 countries. As you may remember from high school biology, the mitochondrion is the battery of the cell. Mitochondria have their own DNA (mtDNA), which helps keep them up and running.
Previous research has shown that at one time in CTVT’s history, the cancer’s cells actually borrowed mtDNA from a dog. When the cancer moved from one dog to another, it took the first dog’s mtDNA along for the ride, which created two separate lines of CTVT: one with new mtDNA and one without. This type of horizontal gene transfer is rare in nature, but it has been known to happen.
Evidently, it happened quite a bit for CTVT. Andrea Strakova of the University of Cambridge is a veterinary scientist and co-author of the new paper. She said in a press statement: “At five distinct time-points in its history, the cancer has 'stolen' mitochondrial DNA from its host, perhaps to help the tumour survive." This is bad news for individual dogs, but an amazing resource for researchers, as it allows them to trace the migration patterns of domesticated dogs across the world.
They can do that because each CTVT lineage, or "clade," arose in a different region of the world. Tracing the movement of these clades provides a pretty good indication of how, and how quickly, dogs have traveled over the last few millennia. One lineage started in Eurasia about 1000 years ago but was in the Americas 500 years later, which suggests the carriers of that particular cancer line belonged to European settlers.
The researchers also found evidence of genetic recombination: that is, the tumors seem to have not only stolen the dogs' mtDNA but also absorbed it, fusing it with their own. This has never been seen before in cancer of any kind, says co-author Máire Ní Leathlobhair, also of Cambridge: "Mitochondrial DNA recombination could be happening on a much wider scale, including in human cancers, but it may usually be very difficult to detect. When recombination occurs in transmissible cancers, two potentially very different mitochondrial DNAs—one from the tumour, one from the host—are merging and so the result is more obvious."
Unwelcome though it may be, CTVT is a remarkable scientific resource, says Cambridge geneticist and senior co-author Elizabeth Murchison: "The genetic changes in CTVT have allowed us to reconstruct the global journeys taken by this cancer over two thousand years. It is remarkable that this unusual and long-lived cancer can teach us so much about the history of dogs, and also about the genetic and evolutionary processes that underlie cancer more generally.”