Clonally Transmissible Cancers in Nature

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While a recent discovery of a series of communicable cancers has raised concerns, there has been no sign of readily transmittable cancer in people that could spread through a population the way the on
While a recent discovery of a series of communicable cancers has raised concerns, there has been no sign of readily transmittable cancer in people that could spread through a population the way the on

The recent discovery of a series of communicable cancers in a variety of animals ― including a second type in a single species ― has raised a chilling concern.

“The possibility that clonally transmissible cancers may arise more frequently in nature than previously considered warrants further investigation of the risk that such diseases could arise in humans,” wrote the researchers who reported the second form of transmissible cancer in Tasmanian devils just two years ago.1

They noted, however, that there has been no sign of readily transmittable cancer in people that could spread through a population the way the ones found in other species do.

“Although transfer of cancer cells between two humans has been reported in rare circumstances, involving injury, organ transplantation, experimental treatments, or pregnancy, no human cancer has been observed to naturally transmit between more than two human hosts.”

Researchers first identified a transmissible cancer in the facial tumors of Tasmanian devils in 1996.2 The disease is spread by the transfer of living cancer cells from one animal to another through biting, which the devils do frequently in fights over mates or food. The cancer cells are able to bypass the infected animal's immune system, causing large tumors on the face or inside the mouth. It is usually fatal within months.

Since it was first detected in the 1990s, devil facial tumor disease (DFTD) has spread to infect nearly 4 out of 5 of the marsupials.3

“The latest census was at a 77% decrease across the total population studied,” said Maximilian Stammnitz, PhD candidate in the department of veterinary medicine at the University of Cambridge in the United Kingdom, and coauthor of a recently published study on the origins and causes of transmissible cancers in devils. “It is believed to threaten the species with extinction.”

Now, communicable cancers have been identified in dogs and certain marine bivalves.

Canine transmissible venereal tumor (CTVT) was first described by a veterinary practitioner in London in 1810, but wasn't identified as a contagious cancer descended from a single line until 2006.4 Spread through the transfer of living cancer cells, usually during mating, CTVT causes tumors on the external genitalia of both male and female dogs. A genetic analysis found that CTVT had gone through nearly 2 million mutations, leading researchers to conclude that the disease “first arose in a dog with low genomic heterozygosity that may have lived approximately 11,000 years ago.”5

In 2015, researchers studying outbreaks of disseminated neoplasia, a fatal leukemia-like cancer causing massive global population loss among marine bivalves, reported that “the genotypes of the neoplastic cells all differ from the genotype of their host animals and are identical or very closely related to each other. We conclude that the individual leukemias are not derived by independent oncogenic transformation of cells within each host but instead come from a single genetically unrelated parent. The data strongly argue that disseminated neoplasia is naturally spreading between animals as a transmissible cancer cell.”6

Remarkably, the authors noted, the cells came from clam beds hundreds of miles apart. And, they added, while the previously known types of transmissible cancers, in dogs and Tasmanian devils, migrated through direct contact between animals the same was not true of the soft-shell clams.

“The mechanism by which the soft-shell leukemic cell line could be transferred from animal to animal in the wild is not clear,” they wrote. “Adult clams are sessile and do not normally come in contact with one another. Clams do filter feed, however, raising the possibility that leukemia engraftment occurs through filtration of seawater contaminated with neoplastic cells.”

While the clam study was underway, a team of researchers found a second transmissible form of facial tumor cancer (DFT2) in five devils in southern Tasmania. DFT2, they wrote, caused “tumors that are grossly indistinguishable but histologically distinct from those caused by DFT1. DFT2 bears no detectable cytogenetic similarity to DFT1 and carries a Y chromosome, which contrasts with the female origin of DFT1.”

The discovery, they continued, “raises the possibility that this species is particularly prone to the emergence of transmissible cancers. More generally, our findings highlight the potential for cancer cells to depart from their hosts and become dangerous transmissible pathogens.”

Despite the seemingly sudden spike in the number of known contagious cancers, such malignancies remain exceedingly rare, and unheard of in humans. In fact, there have been only a small number of known cases in which cancer passed from one person to another.

One 1986 incident involved a 19-year-old laboratory worker at the National Institutes of Health who accidentally stuck herself with a needle while injecting colonic cancer cells into mice. The otherwise healthy woman developed a tumor on her hand.7

Similarly, a decade later, a surgeon who cut himself while removing a malignant fibrous histiocytoma from a patient's abdomen developed a tumor five months later at the site of the original lesion.8 After the tumor was removed, an analysis revealed that it, too, was a malignant fibrous histiocytoma.

A case that confirmed transmission of cancer from a mother to her fetus occurred in Japan in 2007.9 The 28-year-old mother was hospitalized with uncontrollable vaginal bleeding 36 days after the birth. Doctors determined she had leukemia and she died shortly thereafter. When the baby was 11 months old she developed a large leukemic tumor on her cheek, which genetic markers showed to have come from her mother.

Normally, the immune response of humans rejects any allogenic tissue, including cancerous cells. The same is generally true of animals, as well. Transmissible cancers, however, are able to evade the body's natural defenses in animal after animal. The exact means by which they can avoid natural killer cells remains unclear.

While researchers ponder that, the discovery of a second transmissible cancer in the Tasmanian devils raises new questions.

“There were no reports of animals with facial tumors comparable with those caused by DFT1 and DFT2 prior to 1996,” Mr Stammnitz and his colleagues wrote in a paper published in April. “Thus, the recent identification of two transmissible cancers in Tasmanian devils, detected within an interval of 18 years, is very surprising, and suggests that exogenous or anthropogenic factors may contribute to risk of transmissible cancer development specifically in this species.”10

But they found no evidence that the disease was caused by a virus or man-made toxins.

Most likely, Mr Stammnitz said, is that devils have a natural propensity for these cancers and that land use practices and road construction have pushed devils into more heavily populated clusters. Thus, they increase the risk of exposure to devils with cancer, facilitating the spread of both types of facial tumors.

“Maybe cancers just find weak spots in these species' immune systems or they find ways to evolve along with them,” he said. “The truth is we know very little.”

And, he added, while transmissible cancers pose a serious environmental threat to affected species, there is no known danger to humans.

“I don't think we should be very concerned as humans,” Mr Stammnitz said. “In many places around the world, we have such a high population density that if there had been instances we would have likely noticed.”

References

  1. Pye RJ, Pemberton D, Tovar C, Tubio JMC, Dun KA, Fox S, Darby J, Hayes D, Knowles GW, Kreiss A, Siddle HVT, Swift K, Lyons B, Murchison EP, Woods GM. A second transmissible cancer in Tasmanian devils. Proceedings of the National Academy of Sciences Jan 2016, 113 (2) 374-379; DOI:10.1073/pnas.1519691113
  2. Hawkins CE, Baars C, Hesterman H, Hocking GJ, Jones ME, Lazenby B, Mann D, Mooney N, Pemberton D, Pyecroft S, et al. Emerging disease and population decline of an island endemic, the Tasmanian devil Sarcophilus harrisii. Biol. Conservat. 2006; 131: 307–324
  3. Lazenby BT, Tobler MW, Brown WE, et al. Density trends and demographic signals uncover the long‐term impact of transmissible cancer in Tasmanian devils. J Appl Ecol. 2018;55:1368–1379. https://doi.org/10.1111/1365-2664.13088
  4. Strakova A, Murchison EP. The cancer which survived: insights from the genome of an 11 000-year-old cancer. Current Opinion in Genetics & Development. Volume 30, February 2015, Pages 49-55. https://doi.org/10.1016/j.gde.2015.03.005
  5. Murchison EP, Wedge DC, Alexandrov LB, et al. Transmissible dog cancer genome reveals the origin and history of an ancient cell lineage. Science (New York, NY). 2014;343(6169):437-440. doi:10.1126/science.1247167.
  6. Metzger MJ, Reinisch C, Sherry J, Goff SP. Horizontal Transmission of Clonal Cancer Cells Causes Leukemia in Soft-Shell Clams. Cell. Volume 161 , Issue 2 , 255 – 263 DOI: https://doi.org/10.1016/j.cell.2015.02.042
  7. Gugel EA, Sanders ME. Needle-Stick Transmission of Human Colonic Adenocarcinoma. N Engl J Med. Dec. 4, 1986. 1986; 315:1487. DOI: 10.1056/NEJM198612043152314
  8. Gartner H-V, Seidl C, Luckenbach C, Schumm G, et. al. Genetic Analysis of a Sarcoma Accidentally Transplanted from a Patient to a Surgeon. N Engl J Med. 1996; 335:1494-1497. DOI: 10.1056/NEJM199611143352004
  9. Isoda T, Ford AM, Tomizawa D, vanDelft FW, Gonzalez De Castro D, Mitsuiki N, Score J, Taki T, Morio T, Takagi M, Saji H, Greaves M, Mizutani S. Immunologically silent cancer clone transmission from mother to offspring. Proceedings of the National Academy of Sciences. Oct 2009, 106 (42) 17882-17885; DOI:10.1073/pnas.0904658106
  10. Stammnitz MR, Coorens THH, Gori KC, Hayes D, Fu B, Wang J, Martin-Herranz DE, Alexandrov LB, Baez-Ortega A, Barthone S, Beck A, Giordano F, Knowles GW, Kwon YM, Hall G, Price S, Pye RJ, Tubio JMC, Siddle HVT, Sohal SS, Woods GM, McDermott U, Yang F, Garnett MJ, Ning Z, Murchison EP. Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils. Cancer Cell. Volume 33, Issue 4, p607–619.e15, 9 April 2018. DOI: https://doi.org/10.1016/j.ccell.2018.03.013

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