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article imageThe curious story of a dog's cell that turned into a cancer

By Karen Graham     Aug 10, 2019 in Science
A contagious canine cancer that conquered the world by spreading between dogs during mating likely arose around 6,000 years ago in Asia and spread around the globe through maritime activities, scientists say.
A detailed genetic study, published in the journal Science, reveals some surprising, and even mysterious, findings about canine transmissible venereal tumor — a cancer that has survived for thousands of years, having mutated and evolved over time.
This fascinating cancer spreads between dogs through the transfer of living cancer cells, primarily during mating, resulting in genital tumors in both male and female domestic dogs. But what is remarkable about this tumor is that the cancer cells are those of the original dog in which the cancer arose.
The only difference in the modern cancer cells and the cells of the original dog are those that have arisen over time either through spontaneous changes in the cells' DNA or through changes caused by carcinogens.
Ph.D. student, Adrian Baez-Ortega, one of the authors of the study said, “This tumor has spread to almost every continent, evolving as it spreads…changes to its DNA tell a story of where it has been and when, almost like a historical travel journal.”
The study was led by researchers with the Transmissible Cancer Group at the University of Cambridge. The research team studied tumors taken from 546 canines worldwide - comparing the DNA. They created a phylogenetic tree - a type of family tree of the different mutations in the tumors.
The evolutionary process results in constant change - and means that cells at opposite ends of a tumor can be genetically different. By comparing the patterns of mutations and working backward, scientists can identify which mutations arose when and where, and work out how a tumor originated, evolved, and spread.
While this type of examination usually is done from samples taken from a single body, the researchers used samples collected from six continents. “We mapped out a metastasis on a global scale, over thousands of years,” said Elizabeth Murchison of the University of Cambridge, who led the study.
Based on their genetic studies, the research team concluded that all the tumors found in North, Central and South America came from the same origin point from the same introduction event. After being transferred to the Americas about 500 years ago, it is believed that the disease was then spread to Africa and back to India, according to SciTech Europa.
Cancer evolution over thousands of years.
Cancer evolution over thousands of years.
Adrian Baez-Ortega Et al
While the finding shed light on the historical spread of the disease, it is the tumor's evolution that particularly excites the researchers. With recent advances in cancer research, scientists are able to look closer at mutations in tumor cells and identify unique signatures left by carcinogens. This allows them to see, for example, the damage that ultraviolet (UV) light causes.
Using these new techniques, researchers were able to identify the signatures for five different biological processes that have damaged the canine tumor over its history, including exposure to UV light. A new signature - called "Signature A" - has a very distinctive mutational signature, and has never been seen before in a tumor. It caused mutations only in the tumor's distant past, several thousand years ago, and has never been seen since.
"This is really exciting - we've never seen anything like the pattern caused by this carcinogen before," says Dr. Murchison. "It looks like the tumor was exposed to something thousands of years ago that caused changes to its DNA for some length of time and then disappeared. It's a mystery what the carcinogen could be. Perhaps it was something present in the environment when the cancer first arose."
More about Cancer, Canine cancer, CTVT, sexually transmitted, freeliving parasite
 
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