Transmissible Dog Cancer is Oldest Cancer Cell Line

By on February 18, 2014

Scientists have discovered the world’s oldest known cancer cell line, which is estimated to have originated 11,368 years ago. The cancer, canine transmissible venereal tumor (CTVT), is spread between dogs when they copulate. Unlike typical cancers, this cancer does actually spread from one dog to the next, and has done so for about 11,000 years, showing how well-adapted this cancer is to its niche.

Tumor cells were taken from two different dogs that were living in different regions and were different breeds. One tumor was taken from an Aboriginal Camp dog in Australia and the other tumor was taken from an American Cocker Spaniel in Brazil. The genome of each tumor was sequenced; they were found to have similar chromosomal rearrangement.

Specialized genetic tests showed that there were approximately 1.9 million somatic mutations in the genome for CTVT. Around 100,000 mutations were unique to both tumors, indicating that these have arisen more recently, after they diverged during evolution.

CTVT shows mutations that are found in human cancers and are correlated with patient age and exposure to ultraviolet (UV) light. This is bad for dogs, because as the tumor is exposed to sunlight, the UV light will cause mutations. The cells that are exposed to the sunlight and are mutated are the ones that are more likely to be transferred to another dog.

To determine the length of time CTVT has been present on Earth, scientists used human medulloblastoma as a molecular clock, or a model for the rate of mutation. Human medulloblastoma was chosen because it seems to have the most similar correlation between number of mutations and patient age.

CTVT is estimated to have originated 11,368 years ago, but this should be considered with uncertainty. The cancer may not accumulate mutations in a “clock-like” manner, and the rates of mutation may be different in human medulloblastoma and CTVT, despite the similar correlation between mutations and patient age.

The scientists didn’t settle with this, though. They decided to also see how long ago the two tumors they studied shared a common ancestor. Their studies determined that the two tumors most likely diverged about 460 years ago, which is noted to be when the era of human global exploration occurred.

Furthermore, the scientists have even identified information about the dog CTVT originated in. CTVT likely originated a dog that was one of the ancient breeds that is closely related to the Alaskan Malamutes and Huskies. The dog was probably medium- or large-sized, with an agouti (multi-colored bands on each strand of fur) or solid black coat. Due to a mixture of wolf-like and dog-like alleles at loci linked with dog domestication, it is likely that the dog was somewhat domesticated. There was one X chromosome, but no evidence of a Y chromosome, so the gender of the dog is still undetermined.

CTVT most likely arose in a genetically isolated population. The low genetic diversity enabled the cancer to escape the hosts’ immune systems. Only one other transmissible cancer of this nature is known. Like canine transmissible venereal tumor, it arose in a population with low genetic diversity.

Source: http://www.sciencemag.org/content/343/6169/437.full#F1

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