CTVT is primarily spread in dogs through mating, though it can also be spread through licking, sniffing, or giving birth.
CTVT most commonly arises in the form of genital tumors. When an infected dog mates, it passes on living tumor cells. These tumor cells can also be passed on through licking, sniffing, or giving birth.
Arising more than 11,000 years ago from the cells of a single dog - referred to as the "founder dog" - CTVT is one of the oldest known cancers.
According to researchers from the University of Cambridge in the United Kingdom, all CTVT tumors consist of DNA that belongs to the founder dog.
By analyzing the CTVT tumors of dogs across the globe, researchers can pinpoint and analyze mutations that these tumors have acquired over time, enabling them to determine the origins of the disease and when and how it spread.
Building an 'evolutionary family tree' of CTVT
For this latest study - published in eLife - co-first author Andrea Strakova, of the Department of Veterinary Medicine at Cambridge, and colleagues analyzed the DNA of mitochondria in the CTVT tumors of 449 dogs from 39 countries.
Mitochondria are commonly referred to as the "powerhouses" of cells, providing cells with the energy they need to function.
According to Strakova and colleagues, previous studies have suggested that among dogs infected with CTVT, there have been occasions when mitochondrial DNA (mtDNA) has transferred to their tumors.
As such, this mtDNA has been transferred to the tumor cells of dogs that are subsequently infected.
The team's latest analysis of CTVT tumors revealed that the mtDNA transfer process between CTVT-infected dogs and their tumors has occurred at least five times over the past 2,000 years - a process that the researchers suggest may have arisen to aid tumor survival.
This discovery enabled the team to create an "evolutionary family tree" consisting of five branches known as "clades." Each clade represents a point in time when mtDNA was transferred between CTVT-infected dogs and their tumors.
Identifying the geographical location of the tumors within each clade enabled the researchers to pinpoint how CTVT has spread worldwide.
CTVT-infected dogs accompanied humans on travels at sea
The evolutionary family tree suggests that - because of the distance and speed that CTVT spread - dogs often accompanied humans on their sea travels.
"The extensive and recent global expansion detected in the CTVT lineage is consistent with signals of widespread admixture observed in worldwide populations of domestic dogs, highlighting the extent to which canine companions accompanied human travelers on their global explorations," the authors explain.
They point to one clade of the evolutionary tree that suggests CTVT may have spread from Russia or China approximately 1,000 years ago.
However, it is likely that the disease only arose in the Americas around 500 years ago, which suggests that European colonialists - known to have traveled with dogs - brought it with them.
Additionally, the evolutionary tree suggests that CTVT arrived in Australia at the beginning of the 20th century, and that it was likely brought into the country by infected dogs that accompanied European settlers.
The researchers explain their findings further in the video below:
'Recombination' process identified in cancer for the first time
As well as shedding light on the evolutionary history of CTVT, the researchers uncovered interesting information on the mechanisms by which mtDNA transfers to the tumors of dogs with CTVT.
The team found that mtDNA molecules from the healthy cells of CTVT-infected canines that have transferred to tumor cells sometimes mix with the mtDNA within tumor cells - a process referred to as "recombination."
According to Strakova and colleagues, such a process has never before been observed in cancer, and the discovery indicates that it may not only be the cancer cells of dogs that are subject to recombination.
"Mitochondrial DNA recombination could be happening on a much wider scale, including in human cancers, but it may usually be very difficult to detect," says co-first study author Máire Ní Leathlobhair, of the Department of Veterinary Medicine at Cambridge.
"When recombination occurs in transmissible cancers, two potentially very different mitochondrial DNAs - one from the tumor, one from the host - are merging and so the result is more obvious," she explains.
"In human cancer, the tumor's mitochondrial DNA is likely to be very similar to mitochondrial DNA in the patient's normal cells, so the results of recombination would be almost impossible to recognize."
At present, the researchers are unclear what significance this recombination discovery has. Still, they are planning to investigate whether it plays a role in cancer cell survival, and whether inhibiting the process could halt cancer cell growth.
"The genetic changes in CTVT have allowed us to reconstruct the global journeys taken by this cancer over 2,000 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."
Senior author Dr. Elizabeth Murchison