Scientists identify the sea as cancer spread 6000 years ago

Researchers have discovered how cancer spreads around the world between sea dogs around 6,000 years ago in Asia

A detailed genetic study, published today (Aug. 2) in Science, reveals some surprising – and even mysterious – discoveries about how this cancer, which has survived for thousands of years, has mutated and evolved. over time.

The "Canine Transmissible Venereal Tumor" is a cancer that spreads from one dog to another through the transfer of live cancer cells, mainly during mating. The disease usually manifests as bad tumors in domestic male and female dogs. He appeared for the first time in a dog but survived beyond the death of the original dog by spreading to new dogs. Cancer is now present in dog populations around the world and is the oldest and most prolific cancer line known in the wild.

One of the most remarkable aspects of these tumors is that their cells are those of the original dog in which the cancer appeared and not the dog carrier. The only differences between modern dog tumor cells and those of the original tumor are those that have developed over time, either by spontaneous changes in cell DNA or by changes caused by carcinogens.

An international team of researchers, led by scientists from the University of Cambridge's transmissible cancer group, compared the differences in tumors collected from 546 dogs worldwide to understand how this disease appeared and how it was managed to spread throughout the world.

"This tumor has spread to almost every continent and has evolved in parallel," said Adrian Baez-Ortega, a PhD student in the communicable cancer group, part of the Cambridge Department of Veterinary Medicine. "The changes in his DNA tell a story about where he was and when, almost like a historical travel journal."

With the help of data, they created a phylogenetic tree – a genealogical tree type of different mutations in tumors. This allowed them to estimate that cancer first appeared between 4,000 and 8,500 years ago, probably in Asia or Europe. All modern tumors date back to a common ancestor about 1,900 years ago.

The researchers say that cancer was first spread in Europe and the Americas, about 500 years ago, when European settlers arrived for the first time on the continent by sea. Almost all the tumors found today in North, Central and South America are from this one introductory event.

Since the Americas, the disease has spread more in Africa and the Indian subcontinent – almost all the places that were in the days of the European colonies. For example, cancer is observed in Reunion, but this is where European travelers stopped on their way to India. All of this evidence suggests that the tumor was spread by sea dogs transported as part of marine activities.

If the results related to the historical spread of the disease are interesting, it is the evolution of the tumor that particularly excites researchers.

Recent developments in cancer biology have allowed scientists to examine the mutations of tumor DNA and to identify the unique signatures left by carcinogens. This allows them to see, for example, the damage caused by ultraviolet (UV) radiation.

Using these techniques, the researchers identified signatures for five different biological processes that damaged the canine tumor throughout its history. Four of them, including exposure to ultraviolet light, are known processes already linked to human cancers. However, one of them – called "Signature A" – has a very distinctive mutation signature, different from all previously seen: it only caused mutations in the distant past of the tumor, there are several thousand years, and has never been seen since.

"It's really exciting. We have never seen anything similar to what was caused by this carcinogen, "says Dr. Elizabeth Murchison, who leads the Communicable Cancer Group at Cambridge University.

"It seems that the tumor was exposed to something thousands of years ago that changed its DNA for a while before disappearing. It's a mystery of what could be the carcinogen. Maybe it was something present in the environment where the cancer first appeared. "

Another fascinating discovery related to the evolution of tumors. There are two main types of selection in the theory of evolution: positive and negative. Positive breeding is the time when mutations that give an organism a particular benefit are more likely to be pbaded on from generation to generation; Negative selection refers to cases where mutations that may have a deleterious effect are less likely to be transmitted. This selection tends to be by badual reproduction.

When the researchers badyzed the tumors, they found no evidence of positive or negative selection. This implies that the tumor will accumulate more and more potentially damaging mutations over time, making it less and less adapted to its environment.

Baez-Ortega explains:

"Normally, we observe selection pressures acting on the evolution of an organism. Since these canine tumors are foreign bodies, they could be expected to compete with the dog's immune system, transmitting only the strongest tumors. It does not seem to happen here.

"This" parasite "of cancer has been remarkably successful in surviving for thousands of years, but continues to deteriorate. This suggests that his days can be counted – but it will probably take tens of thousands of years to disappear. "

Wellcome, the Leverhulme Trust and the Kennel Club Charitable Trust supported the research.

References

A. Baez-Ortega et al. Somatic evolution and global expansion of an old transmissible cancer line. Science 365, ea9999 (2019). DOI: 10.1126 / science.aau9923.