Scientists have identified a widespread sexually transmitted canine tumor that can be spread from dog to dog. Canine transmissible venereal tumor (CTVT) is likely the oldest known cancer and retains much the same genetic structure it had when it began in a single wolf or dog more than 200 years ago. More broadly, the finding casts doubt on a long-held theory about genetic instability in cancer cells and raises new questions about tumor evolution.
CTVT is a common, usually nonlethal, cancer that affects dogs of all breeds around the world. Scientists once thought it was caused by a transmissible virus, much like cervical cancer in humans, but recent studies suggested the tumor cells themselves are spread from dog to dog, perhaps during sex or through oral contact with tumors.
Probing that theory, virologists led by University College London scientist Robin Weiss took tumor and blood samples from 16 dogs from three countries. DNA analysis revealed strong genetic similarities between the tumors, evidence that the tumor cells came from a common ancestral cell. Furthermore, there was no genetic match between the tumors and the dogs, which would be expected if the tumors arose by mutation of a dog's own cells. After examining the genetic structures of tumors taken from 24 other dogs from five more countries, the team determined that the cancer must have originated in one animal, most likely a gray wolf or an old-breed dog between 200 and 2500 years ago.
Scientists suspect that CTVT first arose in an inbred herd of dogs or wolves, which would have made the dogs' immune systems more receptive to the foreign tissue. Soon after it developed, Weiss says, the cancer split into two subpopulations, both of which are found in dogs today. The cancer most likely was more virulent in the beginning, but Weiss says it seems to have evolved to allow the canine immune system to defeat it--but not before the disease is passed on to another dog. The work appears in the 11 August issue of Cell.
The finding--that a line of cancer cells has existed for more than 200 years--calls into question the notion that cancer cells become more aggressive as they evolve, ultimately becoming genetically unstable and more vulnerable to drugs and the body's immune system, says Weiss. "I think this tumor is telling us to think more broadly about genome stability and genome instability in terms of cancer."
There have been no documented cases of human transmissible cancers; however, there has been another animal case. Last year, scientists in Australia released research suggesting that a facial cancer that has decimated the wild Tasmanian devil population is transmissible (Science, 18 February 2005). There is no relation between the tumors, but there is a shared concern for conservation biologists, says Elaine Ostrander with the U.S. National Human Genome Research Institute in Bethesda, Maryland. "The notion that infectious tumors exist is a whole new concern for threatened or endangered species," she says. "It won't surprise me if there are more cases like this that come along."