In a paper published Thursday in the journal Science, researchers sequenced the genome of tumorous cancer cells from two living dogs located at opposite sides of the planet and determined the genetic makeup of the first, ancient dog to suffer the disease.
The cancer, called canine transmissible venereal tumor, or CTVT, is the oldest and most widely spread cancer on the planet, according to study authors. Prior studies have estimated the illness to be up to 70,000 years old.
The disease, which often appears as a red, cauliflower-like mass on the animal’s genitals, began as a single cell in a single dog. That cell somehow acquired a mutation that caused it to begin making copies of itself. These fast-reproducing cancer cells then managed to survive the ancient dog’s death by transferring to another dog during mating.
“We do not know why this particular individual gave rise to transmissible cancer,” said lead study author Elizabeth Murchison, a genetics researcher at the Wellcome Trust Sanger Institute and the University of Cambridge.
“It spread around the world within the last 500 years, possibly carried by dogs accompanying seafarers on their global expeditions during the dawn of the age of exploration,” she said.
The cancer’s genome revealed an extraordinary number of mutations since the rogue cell first appeared: roughly 2 million, according to Murchison and her colleagues. Mutation counts in human cancers are far lower and range between 1,000 and 5,000.
Researchers based their conclusions on cancer cells taken from two afflicted dogs: an Australian aboriginal camp dog and an American cocker spaniel from Brazil.
By comparing genetic variations in the tumor cells, as well as the genome of the first disease-suffering dog, researchers determined the illness arose about 11,368 years ago, in an inbred dog of undetermined gender.
Researchers wrote that it was most likely an ancient breed of dog, as opposed to a wolf, and was probably akin to an Alaskan Malamute or a husky. The animal, they said, was likely of medium or large size with an agouti or solid back coat.
Researchers also determined that the two living dogs likely had a common ancestor who existed 460 years ago, during a period of great human exploration.
The fact that the first dog who suffered the disease was likely inbred provides a significant clue to the success of the disease. Limited genetic diversity may have “facilitated the cancer’s escape from its hosts’ immune systems,” authors wrote.
CTVT tumors are rarely metastatic, and most will regress within a few months, leaving infected dogs with new immunity, according to cancer geneticists Heidi Parker and Elaine Ostrander, of the NIH’s National Human Genome Research Institute.
“Naturally occurring transmissible tumors are extremely rare,” the pair wrote in an accompanying perspectives piece. “The only other known example is the Tasmanian devil facial tumor disease (DFTD). . Unlike the canine tumor, DFTD is highly virulent, metastasizes readily, and is ultimately fatal.”
Tasmanian devils are a small island species with little genetic diversity and, therefore, have little chance of developing new resistance to the disease.
While neither cancer has the ability to spread to humans, researchers said they warranted investigation. Mike Stratton, the senior author of the dog cancer study and director of the Sanger Institute, said such studies helped scientists to understand the evolution of cancer in general.
“Although transmissible cancers are very rare, we should be prepared in case such a disease emerged in humans or other animals,” he said.
©2014 Los Angeles Times
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