̽��ֱ�� of Cambridge - Elizabeth Murchison

Evolution of two contagious cancers affecting Tasmanian devils underlines unpredictability of disease threat

cg605 — Thu, 20 Apr 2023 18:00:01 +0000

Transmissible cancers, which occur only rarely in the animal kingdom, are spread by the transfer of living cancer cells. In the case of Tasmanian devils, the cells are transferred through biting – a behaviour that is common in devils especially in fights over mates and food.

Tasmanian devils are susceptible to two fatal transmissible cancers called devil facial tumour 1 (DFT1) and devil facial tumour 2 (DFT2) that have caused rapid population decline in recent decades. ̽��ֱ��two cancers both manifest with disfiguring facial tumours.

In a new study, ̽��ֱ�� of Cambridge researchers, together with a global team of scientists from Europe, Australia and the United States, mapped the emergence and mutations of DFT1 and DFT2 and characterised these cancers’ ongoing evolution. ̽��ֱ��findings underline the continued threat that transmissible cancers pose to Tasmanian devils.

̽��ֱ��results are published today in the journal Science.

“ ̽��ֱ��incredible fact that Tasmanian devils have not one, but two, transmissible cancers, makes it possible to compare their evolution, and this gives us new insights into the key mechanisms involved,” said lead author Elizabeth Murchison, Professor of Comparative Oncology and Genetics at the Department of Veterinary Medicine, ̽��ֱ�� of Cambridge.

“By looking at the mutations that have accumulated in these cancers’ DNA, we can trace the origins and evolution of these diseases. Our results show that the two cancers arose through similar processes and that both have striking signals of ongoing evolution. It is difficult to predict how this continued cancer evolution will impact devils.”

̽��ֱ��researchers created an improved ‘reference genome’ – essentially a map of the entire DNA sequence – of the Tasmanian devil and compared this to DNA taken from 119 DFT1 and DFT2 tumours. DFT1 was first observed in 1996 in Tasmania’s northeast and is now widespread throughout Tasmania. DFT2, on the other hand, was first observed in 2014 and remains confined to a small area in Tasmania’s southeast. ̽��ֱ��scientists identified mutations in the tumours and used these to build ‘family trees’ of how the two cancers had each independently arisen and evolved over time.

By tracking mutations the researchers discovered that DFT2 acquired mutations about three times faster than DFT1. As mutations usually occur during cell division, the most likely explanation is that DFT2 is a faster growing cancer than DFT1, say the researchers, underlining the importance of DFT2 as a threat.

“DFT2 is still not widespread in the devil population, and very little is known about it. We were really startled to see just how quickly it was mutating, alerting us to what could be a very unpredictable threat to the devils in the long term,” said Maximilian Stammnitz, first author of the study.

̽��ֱ��team found that DFT1 arose in the 1980s, up to 14 years before it was first observed, whereas DFT2 emerged between 2009 and 2012, only shortly before it was detected.

Mapping the mutations revealed that DFT1 underwent an explosive transmission event shortly after it emerged. This involved a single infected devil transmitting its tumour to at least six recipient devils.

DFT1 has now spread throughout almost the entire devil population and has recently been reported in the far northwest of Tasmania, one of the few remaining disease-free regions of the state.

Researchers also identified for the first time an instance of DFT1 transmission between a mother and the young in her pouch. Additionally, they found that the incubation period – the time between infection and the emergence of symptoms – can in some cases be a year or more. These findings have important implications for conservation scientists working to protect the species.

“I come from Tasmania and love Tasmanian devils – they have a special place in my heart,” said Murchison. “Transmissible cancers pose an unprecedented and unpredictable threat to Tasmanian devils. This research highlights the continuing importance of monitoring and conservation programmes. It also gives us new insights into the evolutionary mechanisms operating in cancer more broadly, including in human cancers.”

̽��ֱ��research was funded by Wellcome, the Gates Cambridge Trust and Eric Guiler Tasmanian Devil Research Grants from the ̽��ֱ�� of Tasmania Foundation.

Reference: M. R. Stammnitz et al. ̽��ֱ��evolution of two transmissible cancers in Tasmanian devils, Science, DOI: 10.1126/science.abq6453

Scientists have traced the family trees of two transmissible cancers that affect Tasmanian devils and have pinpointed mutations which may drive growth of deadly diseases.

Transmissible cancers pose an unprecedented and unpredictable threat to Tasmanian devils.

Professor Elizabeth Murchison

Max Stammnitz

Tasmanian Devil

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Male dogs four times more likely to develop contagious cancer on nose or mouth than females

jg533 — Sun, 03 Jul 2022 23:01:00 +0000

A new study has found that male dogs are four to five times more likely than female dogs to be infected with the oro-nasal form of Canine Transmissible Venereal Tumour.

Researchers think this is because of behavioural differences between the sexes: male dogs spend more time sniffing and licking female dogs’ genitalia than vice versa.

Canine Transmissible Venereal Tumour, or CTVT, is an unusual cancer – it is infectious and can spread between dogs when they come into contact. ̽��ֱ��living cancer cells physically ‘transplant’ themselves from one animal to the other.

CTVT commonly affects dogs’ genitals and is usually transmitted during mating. But sometimes the cancer can affect other areas like the nose, mouth and skin.

In the study, the researchers reviewed a database of almost 2,000 cases of CTVT from around the globe and found that only 32 CTVT tumours affected the nose or mouth. Of these, 27 cases were in male dogs.

“We found that a very significant proportion of the nose or mouth tumours of canine transmissible cancer were in male dogs,” said Dr Andrea Strakova in the ̽��ֱ�� of Cambridge’s Department of Veterinary Medicine, first author of the paper. She performed this study with colleagues from the Transmissible Cancer Group, led by Professor Elizabeth Murchison.

Strakova added: “We think this is because male dogs may have a preference for sniffing or licking the female genitalia, compared to vice versa. ̽��ֱ��female genital tumours may also be more accessible for sniffing and licking, compared to the male genital tumours.”

̽��ֱ��findings are published today in the journal Veterinary Record.

CTVT first arose several thousand years ago from the cells of one individual dog; remarkably, the cancer survived beyond the death of this original dog by spreading to new dogs. This transmissible cancer is now found in dog populations worldwide, and is the oldest and most prolific cancer lineage known in nature.

CTVT isn’t common in the UK, although case numbers have risen in the past decade. This is thought to be linked to the import of dogs from abroad. ̽��ֱ��disease occurs worldwide but is mostly linked to countries with free-roaming dog populations.

“Although canine transmissible cancer can be diagnosed and treated fairly easily, veterinarians in the UK may not be familiar with the signs of the disease because it is very rare here,” said Strakova.

She added: “We think it’s important to consider CTVT as a possible diagnosis for oro-nasal tumours in dogs. Treatment is very effective, using single agent Vincristine chemotherapy, and the vast majority of dogs recover.”

̽��ֱ��most common symptoms of the oro-nasal form of the cancer are sneezing, snoring, difficulty breathing, nasal deformation or bloody and other discharge from the nose or mouth.

Genital cases of CTVT occur in roughly equal numbers of male and female dogs.

Transmissible cancers are also found in Tasmanian Devils, and in marine bivalves like mussels and clams. ̽��ֱ��researchers say that studying this unusual long-lived cancer could also be helpful in understanding how human cancers work.

̽��ֱ��research was funded by the Wellcome and International Canine Health Postgraduate Student Inspiration Awards from the Kennel Club Charitable Trust.

Reference

Strakova, A et al: ‘Sex disparity in oronasal presentations of canine transmissible venereal tumour.’ Veterinary Record, July 2022. DOI: 10.1002/vetr.1794

Sniffing or licking other dogs’ genitalia – the common site of Canine Transmissible Venereal Tumour – can spread this unusual cancer to the nose and mouth.

Although canine transmissible cancer can be diagnosed and treated fairly easily, vets in the UK may not be familiar with the signs of the disease because it is very rare here

Andrea Strakova

CTVT Oronasal Tumours Animation Credit Emma Werner

Jan Allen, AMRRIC

Free-roaming dog.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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̽��ֱ��curious tale of the cancer ‘parasite’ that sailed the seas

cjb250 — Thu, 01 Aug 2019 18:48:46 +0000

A contagious canine cancer that conquered the world by spreading between dogs during mating likely arose around 6,000 years ago in Asia and spread around the globe through maritime activities.

Ancient American dogs almost completely wiped out by arrival of European breeds

cjb250 — Thu, 05 Jul 2018 18:00:52 +0000

But one close relative of these native dogs lives on in an unexpected place – as a transmissible cancer whose genome is that of the original dog in which it appeared, but which has since spread throughout the world.

Using genetic information from 71 archaeological dog remains from North America and Siberia, an international team led by researchers at the ̽��ֱ�� of Oxford, ̽��ֱ�� of Cambridge, Queen Mary ̽��ֱ�� of London, and Durham ̽��ֱ�� showed that ‘native’ (or ‘pre-contact’) American dogs, which arrived alongside people over 10,000 years ago and dispersed throughout North and South America, possessed genetic signatures unlike dogs found anywhere else in the world.

Comparison of ancient and modern American dog genomes, however, demonstrated that these pre-contact American dogs rapidly disappeared following the arrival of Europeans and left little to no trace in modern American dogs.

Senior lead author Dr Laurent Frantz from Queen Mary ̽��ֱ�� and the Palaeogenomics & Bio-Archaeology Research Network (Palaeo-BARN) at Oxford said: “It is fascinating that a population of dogs that inhabited many parts of the Americas for thousands of years, and that was an integral part of so many Native American cultures, could have disappeared so rapidly. Their near-total disappearance is likely due to the combined effects of disease, cultural persecution and biological changes starting with the arrival of Europeans.”

Professor Greger Larson, Director of the Palaeo-BARN at Oxford and senior author of the study, said: “This study demonstrates that the history of humans is mirrored in our domestic animals. People in Europe and the Americas were genetically distinct, and so were their dogs. And just as indigenous people in the Americas were displaced by European colonists, the same is true of their dogs.”

By comparing the ancient and modern genomes, the researchers confirmed that the earliest American dogs were not descended from North American wolves, but likely originated in Siberia, crossing into the Americas during early human migrations.

Lead archaeologist Dr Angela Perri from Durham ̽��ֱ��, co-first author on the study, added: “Archaeological evidence has long suggested that ancient dogs had a dynamic history in the Americas, but the fate of these pre-contact dogs and their relationship to modern American dog populations was largely unknown. Our study confirms that they likely originated in Siberia, crossing the Bering Strait during initial human migrations.”

“In fact, we now know that the modern American dogs beloved worldwide, such as Labradors and Chihuahuas, are largely descended from Eurasian breeds, introduced to the Americas between the 15th and 20th centuries.”

Intriguingly, the study revealed a close link between the genomes of the pre-contact dogs, as the researchers refer to them, and those derived from canine transmissible venereal tumours (CTVT). CTVT is a contagious genital cancer that is spread between dogs by the transfer of living cancer cells during mating. CTVT originated from the cells of a single dog, known as the ‘CTVT founder dog’, that lived several thousand years ago. Remarkably, the research revealed that the dog that first spawned CTVT was closely related to American pre-contact dogs. Overall the results indicate that this cancer, now found worldwide, possesses a genome that is the last remaining vestige of the dog population that was once found all across the Americas.

“It’s quite incredible to think that possibly the only survivor of a lost dog lineage is a tumour that can spread between dogs as an infection,” added Maire Ní Leathlobhair, co-first author, from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge. “Although this cancer’s DNA has mutated over the years, it is still essentially the DNA of that original founder dog from many thousands of years ago.”

Co-author and zooarchaeologist Professor Keith Dobney from the ̽��ֱ�� of Liverpool, who co-directs the dog domestication project with Professor Larson added “This is yet another new and exciting finding from our combined genetic and archaeological research, which continues to challenge and illuminate our understanding of the history of the first and most iconic domestic animal.”

̽��ֱ��research was largely funded by Wellcome, the Natural Environment Research Council, and the European Research Council.

Reference
Ní Leathlobhair, M, Perri, AR, Irving-Pease, EK, Witt, KE, Linderholm, A, et al. ̽��ֱ��Evolutionary History of Dogs in the Americas. Science; 6 July 2018; DOI: 10.1126/science.aao4776

̽��ֱ��arrival of Europeans to the Americas, beginning in the 15th century, all but wiped out the dogs that had lived alongside native people on the continent for thousands of years, according to new research published today in Science.

It’s quite incredible to think that possibly the only survivor of a lost dog lineage is a tumour that can spread between dogs as an infection

Maire Ní Leathlobhair

Del Baston (courtesy of the Center for American Archeology)

Ancient dog burial

Yes

Human anti-cancer drugs could help treat transmissible cancers in Tasmanian devils

cjb250 — Mon, 09 Apr 2018 15:57:27 +0000

̽��ֱ��research also found that the two Tasmanian devil transmissible cancers are very similar to each other, and likely both arose due to susceptibilities inherent to the devils themselves.

Tasmanian devils are marsupial carnivores endemic to the Australian island of Tasmania. ̽��ֱ��species is considered endangered due to devil facial tumour 1 (DFT1), a cancer that is passed between animals through the transfer of living cancer cells when the animals bite each other. DFT1 causes grotesque and disfiguring facial tumours, which usually kill affected individuals.

̽��ֱ��DFT1 cancer first arose in a single individual devil several decades ago, but rather than dying together with this devil, the cancer survived by ‘metastasising’ into different devils. Therefore, the DNA of the devils’ tumour cells is not their own DNA, but rather belongs to the individual devil that first gave rise to DFT1 all those years ago. Remarkably, DFT1 cells can escape the devils’ immune systems despite being in essence a foreign body.

̽��ֱ��DFT1 cancer was first observed in north-east Tasmania in 1996, but has subsequently spread widely throughout the island, causing significant declines in devil populations.

In 2014, routine diagnostic screening revealed a second transmissible cancer in Tasmanian devils, devil facial tumour 2 (DFT2), which causes facial tumours indistinguishable to the naked eye from those caused by DFT1, and which is probably also spread by biting. However, analysis showed that the two types of cancer differ at a biological level, and whereas DFT1 first arose from the cells of a female devil, DFT2 appears to have first arisen from a male animal. For now, DFT2 appears to be confined to a peninsula in Tasmania’s south-east.

“ ̽��ֱ��discovery of a second transmissible cancer in Tasmanian devils was a huge surprise,” says Dr Elizabeth Murchison from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge. “Other than these two cancers, we know of only one other naturally occurring transmissible cancer in mammals – the canine transmissible venereal tumour in dogs, which first emerged several thousand years ago.”

In fact, outside of mammals, only five transmissible cancers have been observed, all of which cause leukaemia-like diseases in clams and other shellfish.

“ ̽��ֱ��scarcity of transmissible cancers suggests that such diseases emerge rarely,” she adds. “Before 1996, no one had observed them in Tasmanian devils, so finding two transmissible cancers in Tasmanian devils in just eighteen years was very surprising.”

In order to see whether the devil transmissible cancers are caused by external factors or whether the animals were just particularly susceptible to developing these cancers, a research team led by Dr Murchison analysed the genetic profiles of DFT1 and DFT2 tumours taken from a number of Tasmanian devils. ̽��ֱ��results are published today in the journal Cancer Cell.

̽��ֱ��team found striking similarities in tissues-of-origin, genetics, how the cancer cells mutate, and possible drug targets. This implies that the two tumours belong to the same cancer type and arose via similar mechanisms.

̽��ֱ��team studied the genetic and physical features of the tumours, and compared the two lineages with each other and with human cancers. In doing so, they identified an important role in the tumours for particular types of molecules known as receptor tyrosine kinases (RTKs) in sustaining growth and survival of DFT cancers.

Importantly, drugs targeting RTKs have already been developed for human cancer, and the researchers showed that these drugs efficiently stopped the growth of devil cancer cells growing in the lab. This leads to hope that it may be possible to use these drugs to help Tasmanian devils.

First author of the study, Maximilian Stammnitz, adds: “Altogether, our findings suggest that transmissible cancers may arise naturally in Tasmanian devils. We found no DNA-level evidence of these cancers being caused by external factors or infectious agents such as viruses. It seems plausible that similar transmissible cancers may have occurred in the past, but escaped detection, perhaps because they remained in localised populations, or because they existed prior to the arrival of Europeans in Tasmania in the nineteenth century.”

Why Tasmanian devils should be particularly susceptible to the emergence of DFTs is not clear. However, devils bite each other frequently around the facial area, often causing significant tissue injury. Given the important role for RTK molecules in wound healing, the researchers speculate that DFT cancers may arise from errors in the maintenance of proliferative cells involved in tissue repair after injury.

“When fighting, Tasmanian devils often bite their opponent’s face, which may predispose these animals to the emergence of this particular type of cancer via tissue injury,” adds Stammnitz. “As biting occurs on the face, this would simultaneously provide a route of cell transmission.”

̽��ֱ��researchers say it is also possible that human activities may have indirectly increased the risk of the emergence or spread of transmissible devil facial tumours (DFTs) in recent years. For instance, it is possible that some modern land use practices may have provided favourable conditions for devils, leading to an increase in local population densities of devils, and to greater competition, interactions and fights between animals, which may in turn have raised probabilities of DFTs arising or spreading. Alternatively, early persecution of devils by European colonists may have additionally contributed to this species' documented low genetic diversity, a possible risk factor for disease spread and the ability of DFTs to escape the immune system.

̽��ֱ��researchers also identified deletions in DFT1 and in DFT2 in genes involved in recognition of cancer cells by the immune system. This may help explain how these cancers escape the immune system.

“ ̽��ֱ��story of Tasmanian devils in recent years has been a very concerning one,” says Dr Murchison. “This study gives us optimism that anti-cancer drugs that are already in use in humans may offer a chance to assist with conservation efforts for this iconic animal.”

̽��ֱ��research was funded by Wellcome, the National Science Foundation, Save the Tasmanian Devil Appeal, Leverhulme Trust, Cancer Research UK and Gates Cambridge Trust.

Reference
Stammnitz, M.R., et al. (2018). ̽��ֱ��origins and vulnerabilities of two transmissible cancers in Tasmanian devils. Cancer Cell 33(4), 607-619.

Transmissible cancers are incredibly rare in nature, yet have arisen in Tasmanian devils on at least two separate occasions. New research from the ̽��ֱ�� of Cambridge identifies key anti-cancer drugs which could be trialled as a treatment for these diseases, which are threatening Tasmanian devils with extinction.

This study gives us optimism that anti-cancer drugs that are already in use in humans may offer a chance to assist with conservation efforts for this iconic animal

Elizabeth Murchison

Could cancer drugs help save the Tasmanian devil?

Mathias Appel

Tasmanian devil

Researcher profile: Maximilian Stammnitz

One of Maximilian Stammnitz’s best memories at Cambridge has been his encounter with Tasmanian devils on a field trip to Tasmania in 2016. “There is nothing more exciting than examining actual devils in the wild – they are truly majestic animals!” he says.

Stammnitz is a Gates Cambridge Scholar at Cambridge’s Department of Veterinary Medicine. Originally from “Germany's sunniest spot: Heidelberg”, he came to Cambridge to join the Computational Biology MPhil program at the Department of Applied Mathematics and Theoretical Physics in 2014.

“This course provides fascinating opportunities to study biology through a big data lens, and to learn about vastly emerging genomics technologies from experts in the field,” he says. “ ̽��ֱ��DNA-level expertise and collaboration at Cambridge surrounding topics of genetics, evolution, medicine and computational data analysis is breath-taking.”

It was a seminar by Elizabeth Murchison on transmissible cancers that caught his imagination, however, and he subsequently joined her group at Veterinary Medicine for a summer internship, and then as a PhD student and Gates Cambridge Scholar. ̽��ֱ��ultimate aim of his work is to save the largest carnivorous marsupial on the planet, but by studying the fundamental processes of cancer development in Tasmanian devils, his work could help us understand better how cancer develops in humans.

“I spend most of my working days behind a computer screen, processing and analysing large volumes of DNA and RNA sequencing data from Tasmanian devil tumour biopsies,” he says. “Occasionally, I also do molecular biology experiments in the 'wet lab', to validate our computational results or to establish testing protocols for the devils.”

It isn’t all about work, though. “Over the past year, I have been the captain of our university's Blues men's volleyball team and co-founded PuntSeq, a citizen science project aiming at cost-effective pathogen surveillance of our house river Cam's water,” he says.

“My biggest challenge of living here is to balance truly focused work life and quiet time with the many inspiring distractions that wait behind the corners of Cambridge's old walls. It’s a luxury problem to have as a PhD student.”

Follow Maximilian Stammnitz on Twitter @DevilsAdvoMax

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

A shaggy dog story: ̽��ֱ��contagious cancer that conquered the world

cjb250 — Mon, 16 May 2016 23:01:16 +0000

‘Canine transmissible venereal tumour’ (CTVT) is a cancer that spreads between dogs through the transfer of living cancer cells, primarily during mating. ̽��ֱ��disease usually manifests as genital tumours in both male and female domestic dogs. ̽��ֱ��cancer first arose approximately 11,000 years ago from the cells of one individual dog; remarkably, it survived beyond the death of this original dog by spreading to new dogs. ̽��ֱ��cancer is now found in dog populations worldwide, and is the oldest and most prolific cancer lineage known in nature.

In a study published today in the journal eLife, an international team led by researchers at the ̽��ֱ�� of Cambridge studied the DNA of mitochondria – the ‘batteries’ that provide cells with their energy – in 449 CTVT tumours from dogs in 39 countries across six continents. Previous research has shown that at occasional points in history, mitochondrial DNA has transferred from infected dogs to their tumours – and hence to tumour cells in subsequently-infected dogs.

In the new study, the researchers show that this process of swapping mitochondrial DNA has occurred at least five times since the original cancer arose. This discovery has allowed them to create an evolutionary ‘family tree’, showing how the tumours are related to each other. In addition, the unusual juxtaposition of different types of mitochondrial DNA within the same cell unexpectedly revealed that cancer cells can shuffle or ‘recombine’ DNA from different mitochondria.

“At five distinct time-points in its history, the cancer has ‘stolen’ mitochondrial DNA from its host, perhaps to help the tumour survive,” explains Andrea Strakova, from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge, co-first author of the study. “This provides us with a set of unique genetic tags to trace how dogs have travelled the globe over the last few hundred years.”

In the evolutionary ‘family tree’, the five main branches are known as ‘clades’, each representing a point in history when mitochondria transferred between dog and tumour. By mapping tumours within these clades to the geographical location where they were found, the researchers were able to see how the cancers have spread across the globe. ̽��ֱ��distance and speed with which the clades have spread suggests that the dogs commonly travelled with human companions, often by sea.

One branch of the CTVT evolutionary tree appears to have spread from Russia or China around 1,000 years ago, but probably only came to the Americas within the last 500 years, suggesting that it was taken there by European colonialists. Conquistadors are known to have travelled with dogs – contemporary artworks have portrayed them both as attack dogs and as a source of food.

Image: 1598 fictional engraving by Theodor de Bry supposedly depicting a Spaniard feeding Indian children to his dogs. Wikipedia

̽��ֱ��disease probably arrived in Australia around the turn of the twentieth century, most likely imported inadvertently by dogs accompanying European settlers.

One of the most surprising findings from the study related to how mitochondrial DNA transfers – and mixes – between the tumour and the host. ̽��ֱ��researchers found that mitochondrial DNA molecules from host cells that have migrated into tumour cells occasionally fuse with the tumour’s own mitochondrial DNA, sharing host and tumour DNA in a process known as ‘recombination’. This is the first time this process has been observed in cancers.

Máire Ní Leathlobhair, the study’s co-first author, explains: “Mitochondrial DNA recombination could be happening on a much wider scale, including in human cancers, but it may usually be very difficult to detect. When recombination occurs in transmissible cancers, two potentially very different mitochondrial DNAs – one from the tumour, one from the host – are merging and so the result is more obvious. In human cancer, the tumour’s mitochondrial DNA is likely to be very similar to the mitochondrial DNA in the patient’s normal cells, so the result of recombination would be almost impossible to recognise.”

Although the significance of mitochondrial DNA recombination in cancer is not yet known, its discovery is now leading scientists to explore how this process may help cancer cells to survive – and if blocking it may stop cancer cells from growing.

Dr Elizabeth Murchison, senior author of the study, said: “ ̽��ֱ��genetic changes in CTVT have allowed us to reconstruct the global journeys taken by this cancer over two thousand years. It is remarkable that this unusual and long-lived cancer can teach us so much about the history of dogs, and also about the genetic and evolutionary processes that underlie cancer more generally.”

̽��ֱ��research was funded by the Wellcome Trust, the Leverhulme Trust and the Royal Society.

Reference
Strakova, A et al. Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer. eLife; 17 May 2016; DOI: 10.7554/eLife.14552

A contagious form of cancer that can spread between dogs during mating has highlighted the extent to which dogs accompanied human travellers throughout our seafaring history. But the tumours also provide surprising insights into how cancers evolve by ‘stealing’ DNA from their host.

It is remarkable that this unusual and long-lived cancer can teach us so much about the history of dogs, and also about the genetic and evolutionary processes that underlie cancer more generally

Elizabeth Murchison

Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer

̽��ֱ�� of Cambridge

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Second contagious form of cancer found in Tasmanian devils

cjb250 — Mon, 28 Dec 2015 20:00:13 +0000

̽��ֱ��discovery, published in the journal Proceedings of the National Academy of Science, calls into question our current understanding of the processes that drive cancers to become transmissible.

Tasmanian devils are iconic marsupial carnivores that are only found in the wild on the Australian island state of Tasmania. ̽��ֱ��size of a small dog, the animals have a reputation for ferocity as they frequently bite each other during mating and feeding interactions.

In 1996, researchers observed Tasmanian devils in the north-east of the island with tumours affecting the face and mouth; soon it was discovered that these tumours were contagious between devils, spread by biting. ̽��ֱ��cancer spreads rapidly throughout the animal’s body and the disease usually causes the death of affected animals within months of the appearance of symptoms. ̽��ֱ��cancer has since spread through most of Tasmania and has triggered widespread devil population declines. ̽��ֱ��species was listed as endangered by the International Union for Conservation of Nature in 2008.

To date, only two other forms of transmissible cancer have been observed in nature: in dogs and in soft-shell clams. Cancer normally occurs when cells in the body start to proliferate uncontrollably; occasionally, cancers can spread and invade the body in a process known as 'metastasis'; however, cancers do not normally survive beyond the body of the host from whose cells they originally derived. Transmissible cancers, however, arise when cancer cells gain the ability to spread beyond the body of the host that first spawned them, by transmission of cancer cells to new hosts.

Now, a team led by researchers from the ̽��ֱ�� of Tasmania, Australia, and the ̽��ֱ�� of Cambridge, UK, has identified a second, genetically distinct transmissible cancer in Tasmania devils.

“ ̽��ֱ��second cancer causes tumours on the face that are outwardly indistinguishable from the previously-discovered cancer,” said first author Dr Ruth Pye from the Menzies Institute for Medical Research at the ̽��ֱ�� of Tasmania. “So far it has been detected in eight devils in the south-east of Tasmania.”

“Until now, we’ve always thought that transmissible cancers arise extremely rarely in nature,” says Dr Elizabeth Murchison from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge, a senior author on the study, “but this new discovery makes us question this belief.

"Previously, we thought that Tasmanian devils were extremely unlucky to have fallen victim to a single runaway cancer that emerged from one individual devil and spread through the devil population by biting. However, now that we have discovered that this has happened a second time, it makes us wonder if Tasmanian devils might be particularly vulnerable to developing this type of disease, or that transmissible cancers may not be as rare in nature as we previously thought.”

Professor Gregory Woods, joint senior author from the Menzies Institute for Medical Research at the ̽��ֱ�� of Tasmania, adds: “It’s possible that in the Tasmanian wilderness there are more transmissible cancers in Tasmanian devils that have not yet been discovered. ̽��ֱ��potential for new transmissible cancers to emerge in this species has important implications for Tasmanian devil conservation programmes.”

̽��ֱ��discovery of the second transmissible cancer began in 2014, when a devil with facial tumours was found in south-east Tasmania. Although this animal’s tumours were outwardly very similar to those caused by the first-described Tasmanian devil transmissible cancer, the scientists found that this devil’s cancer carried different chromosomal rearrangements and was genetically distinct. Since then, eight additional animals have been found with the new cancer in the same area of south-east Tasmania.

̽��ֱ��research was primarily supported the Wellcome Trust and the Australian Research Council, with additional support provided by Dr Eric Guiler Tasmanian Devil Research Grants and by the Save the Tasmanian Devil Program.

For more information about the research into Tasmanian devils, see T is for Tasmanian Devil.

Reference
Pye, RJ et al. A second transmissible cancer in Tasmanian devils. PNAS; 28 Dec 2015

Transmissible cancers – cancers which can spread between individuals by the transfer of living cancer cells – are believed to arise extremely rarely in nature. One of the few known transmissible cancers causes facial tumours in Tasmanian devils, and is threatening this species with extinction. Today, scientists report the discovery of a second transmissible cancer in Tasmanian devils.

Until now, we’ve always thought that transmissible cancers arise extremely rarely in nature, but this new discovery makes us question this belief

Elizabeth Murchison

Gopal Vijayaraghavan

Tassie devil orphan

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Tasmanian Devils and the transmissible cancer that threatens their extinction

amb206 — Wed, 14 Oct 2015 11:05:42 +0000

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In 1996 a wildlife photographer working in a remote part of Tasmania noticed a ‘Tassie devil’ (the affectionate name for the Tasmanian devil) with a tumour on its face. He assumed that the animal’s facial disfigurement was a one-off – but within a year he spotted another devil with a similar problem. He notified the authorities and, as increasing numbers of affected devils were seen, it was established that the animals were suffering from a wave of devastating facial tumours.

Ten years after the first tumour was spotted, scientists revealed that the lesions weren’t ordinary tumours. They were caused by a transmissible cancer – an extremely rare type of disease, in which living cancer cells are physically transmitted between animals. Only three transmissible cancers are known in nature, and these affect dogs, clams and Tasmanian devils respectively. In the case of devils, the cancer cells are thought to be transmitted by biting.

Once they have acquired the cancer, devils usually live just a matter of months. No treatment exists. As the number of sightings of afflicted animals continued to escalate, with the disease moving across the island from east to west, it became clear that the Tasmanian devil was threatened with extinction.

Dr Elizabeth Murchison, a specialist in comparative oncology and genetics at the ̽��ֱ�� of Cambridge’s Department of Veterinary Medicine, was brought up in Tasmania. ̽��ֱ��presence of Tasmanian devils – which are the emblem of the Tasmanian state – was part of her rural childhood. Devils are scavengers and, by disposing of dead animals, they provide a useful service as the ‘garbage bins of the bush’.

Murchison studied genetics and biochemistry at the ̽��ֱ�� of Melbourne, and then studied for her PhD in molecular biology at Cold Spring Harbor Laboratory, New York. Her interest in solving the puzzle of the tumours began in 2006 when she came across a roadkill devil with a tumour in a wild area of Tasmania. This confronting finding triggered her desire to understand this strange disease.

Her specialism is cancer genetics; her research focuses on developing an understanding of the evolution of the DNA of transmissible cancer by tracing it backwards in time to track the steps by which a normal cell mutates to become a cancerous one.

In 2012, while working at the Sanger Institute, near Cambridge, Murchison led a collaborative group of scientists using new DNA sequencing technologies to unlock the Tasmanian devil genome, as well as the genome of the devils’ transmissible cancer. This research led to the discovery that the Tasmanian devil cancer probably emerged relatively recently in a single female Tasmanian devil. ̽��ֱ��cells derived from this cancer have continued to survive by “metastasising” through the Tasmanian devil population.

More recently, Murchison has concentrated on understanding the genetic differences between tumours occurring in different Tasmanian devils. Although tumours in all Tasmanian devils are a “clone”, derived from the same original animal, the cancer lineage has diverged and acquired new mutations during its spread through the devil population.

This work requires close collaboration with many scientists, especially those back in her native Tasmania. She says: “I wake up to emails from the other side of the world, updating me on the progress of field work back in Tasmania. We skype regularly because working closely together as an interdisciplinary team is the best way to try to understand this disease and help the devils as soon as possible.”

In addition to working on the Tasmanian devil, Murchison’s group studies canine transmissible venereal tumour (CTVT). CTVT is a sexually transmitted genital cancer, spread by the transfer of living cancer cells between dogs. In contrast to the devil cancer, which emerged relatively recently, CTVT probably emerged thousands of years ago. ̽��ֱ��disease has now spread widely and affects dogs around the world. Murchison’s group has recently sequenced the genome of CTVT, and this work has shed light on the evolution of a unique cancer.

One of the most disquieting aspects of transmissible cancers is the fact that they are, effectively, parasites. Once the devil cancer cells are introduced to a new host by means of a bite, they go undetected by the devil’s immune system and thus flourish, eventually killing the animal. By sequencing samples of DNA taken from the devil cancer from 2003 onwards, Murchison is trying to understand how this cancer evolved and changed with time. Her research makes a valuable contribution to the potential development of a vaccine or other therapy to protect devils against the disease.

Over the past decade, the Tasmanian authorities have worked hard to safeguard the future of the Tasmanian devil. An ‘insurance’ population of healthy devils has been spread among Australian parks and zoos. Most recently, a colony of unaffected devils has been established on Maria Island, a national park off the coast of eastern Tasmania.

“Research into this devastating disease in Tasmanian devils is starting to illuminate the underlying processes that caused this unusual disease and promoted its transmission. We hope that our research may also help us to understand basic processes that underlie cancer evolution more generally, including in humans. But, of course, we are motivated by the goal that our research will help to protect this unique and iconic marsupial from extinction,” said Murchison.

Next in the Cambridge Animal Alphabet: U is for an animal used in heraldry since the 15th century and in recipes for anti-poison since the 1700s.

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Inset images: Tasmanian devil with facial tumours (Elizabeth Murchison); Video clips courtesy of the Save the Tasmanian Devil Program , DPIPWE; Tasmanian devil (Joe Le Nevez).

The Cambridge Animal Alphabet series celebrates Cambridge's connections with animals through literature, art, science and society. Here, T is for Tasmanian Devil and the researchers studying the transmissable cancer that threatens these marsupials with extinction.

We are motivated by the goal that our research will help to protect this unique and iconic marsupial from extinction

Elizabeth Murchison

Tasmanian Devil

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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