A new paper from the Transmissible Cancer Group at the University of Cambridge Department of Veterinary Medicine reveals how a transmissible cancer has spread through the Tasmanian devil population, and how this cancer’s genome has evolved and diversified during it evolution.

Tasmanian devil facial tumour 1 (DFT1) is a transmissible cancer threatening Tasmanian devils, marsupial carnivores endemic to the Australian island of Tasmania. DFT1 is one of the few known directly contagious transmissible cancers in nature: it spreads between animals by the transfer of living cancer cells by biting. The disease causes horrifying facial tumours and is usually fatal. First observed in 1996, DFT1 has caused rapid declines in the Tasmanian devil population.

The new research, published in PLOS Biology, annotates genetic changes that have occurred in 648 DFT1 tumours collected from devils throughout Tasmania between 2003 and 2018. These mutations are largely irreversible and can be used as “tags”, which the researchers used to trace the geographical spread of the cancer. This revealed that DFT1 split early into five groups, only three of which have continued to survive. The patterns of DFT1 spread are consistent with epidemiological evidence suggesting that the DFT1 cancer first arose from the cells of a devil that lived in Tasmania’s north-east before quickly colonising areas of central and eastern Tasmania. The new research tracks the cancer’s more recent routes out of this region, and traces the movements of diseased devils over twenty years.

Beyond their use as “tags”, the mutations in the DFT1 genome provide insight into the molecular and evolutionary processes that cause and alter the frequencies of mutations. The researchers found that some mutations occurred repeatedly, suggesting that their presence may provide an advantage to the cancer. One particularly complex series of genetic alterations was observed almost every time DFT1 cells were extracted from devils and grown in a laboratory dish, suggesting that laboratory conditions strongly favour these mutations’ presence. Overall, however, the researchers were surprised by how few mutations were found in DFT1. Indeed, more mutations frequently distinguish two tumours derived from the same cancer within a single human patient than were found between pairs of DFT1 tumours sampled hundreds of kilometres and more than a decade apart.

“DFT1 has acquired relatively few mutations during its thirty-year history,” said Prof Elizabeth Murchison, who led the study. “This research illustrates how a comparatively simple and stable cancer can colonise diverse niches and devastate a species.”

Our latest study on selfish mitochondria in the canine transmissible venereal tumour (CTVT) was recently published in Nature Communications. How did this discovery come about? What were the major turning points in our research? Are you interested to look behind the scenes of this latest CTVT article?

You can read more in the Story behind the paper recently published on the Nature Research Cancer Community website.

A new study by the Transmissible Cancer Group published in Nature Communications today!

Previous research has shown that at several points in history, mitochondria - which are compartments providing cells with their energy - from unrelated host dogs have been captured by CTVT, perhaps to aid survival of this long-lived cancer lineage. The capture of mitochondrial DNA (mtDNA) by canine transmissible venereal tumour (CTVT) creates a unique opportunity to understand the competitive dynamics of two types of mtDNA juxtaposed within the same cell.

In a new study, published in Nature Communications today, we show that one particular type of mtDNA - named A1d1a - has been recurrently captured by CTVT cancer cells on eleven independent occasions. A1d1a is highly over-represented for CTVT mitochondrial capture compared with its frequency in the dog population. Genetic analysis of this mitochondrial type revealed the presence of an insertion at position 16660 of the mtDNA, which appears to reduce transcription - or the reading - of the mtDNA. We propose that A1d1a mitochondria unexpectedly win the race through a ‘selfish’ replicative advantage - by replicating more efficiently - rather than by providing a functional advantage. Apart from providing insights into the characteristics enabling the spread of this cancer that has ‘metastasised’ on a global scale, this work is of much broader importance, as understanding the competitive dynamics of mtDNA is crucial for advancing knowledge of mtDNA genetic disease and assessing the risks of therapeutic mtDNA transplantation in human embryos.

A model explaining repeated CTVT capture of the A1d1a mitochondria. (1) Different types of mitochondria are captured by CTVT cells, (2) but A1d1a mitochondria have a specific insertion at position 16660 of the mtDNA, (3) causing reduction in transcription – or the reading of – the mtDNA in A1d1a, (4) suggesting that A1d1a wins the competition through a replicative (rather than functional) advantage.

This work was carried out at the Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge. Thanks to veterinary collaborators from across the globe, the team collected and analysed 539 CTVT tumours from 43 countries in this study. If you would be interested to participate in future studies carried out by the Transmissible Cancer Group as a collaborator through collecting CTVT samples, or if you have any further questions, please, do not hesitate to contact us!

Article citation: Strakova, A. et al. Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer. Nat Commun 11, 3059 (2020).

The article is featured in the Nature Communications Editors’ Highlights!

Interested further? See where this story began:

Many congratulations to Adrian Baez-Ortega, who won Weintraub Graduate student Award for 2020!

The Harold M. Weintraub Graduate Student Award recognizes outstanding achievement during graduate studies in the biological sciences. This is a very prestigious international graduate student award from the US!  Awardees will participate in a scientific symposium honoring Weintraub and his commitment to innovative science. The award symposium will take place May 1, 2020, at Fred Hutch's Robert W. Day Campus. Adrain will go to Seattle for the award ceremony in May. Well done Adrain!

https://en.wikipedia.org/wiki/Harold_M._Weintraub

TCG second PhD, Dr. Maire Ni Leathlobhair, was officially graduated!

Maire obtained her PhD from Cambridge in 2018 and used computational and statistical modelling of genomic data to understand the origin and evolution of transmissible cancer. She is currently a post-doctoral researcher in the Cancer Genomics group led by Dr David Wedge at the Oxford Big Data Institute.

Many congratulations to Maire from all TCG members and we wish her all the best at her new job in Oxford!

Dr. María Verónica Brignone is a Vet from Argentina, who has collected CTVT tumour biopsies from dogs in Argentina and hosted a visit from a TCG PhD at Argentina previously. During her 2 weeks visit in September, Maria extracted genomic DNA from these CTVT samples and performed PCR analysis for genetic analysis to determine how CTVT in Argentina differs from CTVT tumours collected from other countries. Maria also gave a very interesting presentation of her work at TCG lab meeting and went on our Annual TCG punting trip with us!

We are very pleased that Maria enjoyed her visit at Cambridge and wish we will continue to collaborate with her and her colleagues at Argentina in the future!

Many congratulations to Adrian Baez-Ortega's new paper published on Science 2nd August 2019!

"Somatic evolution and global expansion of an ancient transmissible cancer lineage"

Well done Adrian and the team!

Here are some links to the news about the paper:

Congratulations to Adrian Baez-Ortega , who has been awarded the 2019 Canine Health Awards Postgraduate Student Inspiration Award from the Kennel Club. Adrian will receive £10,000, which he will use to support research on CTVT. Find more information about the award here.

TCG science has recently featured in several books and news articles. An article in the Süddeutsche Zeitung profiled Elizabeth Murchison and her research on transmissible cancers. Transmissible cancers, and TCG science, were covered in Carl Zimmer's new book on heredity She has her mother's laugh. Máire Ní Leathlobhair's recent paper on the origin of CTVT was covered in the popular press, including an interesting article in the New York Times. 

Stay tuned for more TCG news!

Sarah Cox, a pre-clinical Cambridge vet student who performed a summer project at TCG has been awarded a BBSRC studentship.

The UK Veterinary Summer Studentship Programme aims to inspire UK veterinary undergraduates to consider a career in research by funding summer studentships to be undertaken in world-class research environments in any BBSRC eligible institute. 

Congratulations, Sarah!

This summer, TCG members Elizabeth Murchison, Max Stammnitz, Young Mi Kwon and Kevin Gori spent a few weeks in Tasmania performing Tasmanian devil field work. They joined devil trapping trips in the Channel Peninsula, where both DFTDs (DFT1 and DFT2) are present, and in the Freycinet Peninsula on Tasmania's East Coast. They saw many devils, both healthy and diseased, and shared scientific results and findings with collaborators.

Soheil Afshari, a student at the Department of Veterinary Medicine, Garmsar University, Iran, recently visited TCG from 9th July – 23rd July, 2018.
Soheil collected CTVT tumour biopsies from dogs in Iran. During his visit, Soheil extracted genomic DNA from these CTVT samples, performed PCR and genetic analysis to determine how CTVT in Iran differs from CTVT tumours collected from other countries. He also gave an presentation of his work at the end of his visit.

Well done Soheil, we wish you all the best for your PhD!

New research from TCG reveals that the canine transmissible venereal tumour (CTVT) first emerged from a dog that was closely related to an intriguing group of ancient North American dogs. 

The research, published in Science, reports that dogs arrived into North America together with people more than 10,000 years ago. By sequencing ancient DNA from dog bones collected from many sites across North America, we found that these dogs belong to a single genetic lineage that is related to modern-day Arctic breeds, such as huskies. Remarkably, however, these dogs appear to have largely disappeared since the arrival of Europeans 500 years ago.

One genetic legacy of these dogs does remain however: CTVT first arose from an animal that was related to these native American dogs. Thus, this worldwide cancer may be the closest remaining genetic vestige of a group of dogs that once roamed a continent.

Congratulations to Máire Ní Leathlobhair, co-first author on the study. The work was a large collaboration including scientists at the Universities of Cambridge, Oxford and Durham.

Our collaborator from South Africa, Mirjam van der Wel, gave a presentation "Canine transmissible venereal tumours" at the EASTERN CAPE VETERINARY CONGRESS on 4th of May 2018. It was well received by the audience and we are grateful that M. is spreading the knowledge of CTVT and our research amongst the clinical veterinary audience. Thank you for your enthusiasm, and congratulations, Mirjam! If you would also be interested to get involved in our research by collecting samples, see the following page for further info https://www.tcg.vet.cam.ac.uk/Research/get-involved-in-CTVT-research

WELL DONE Mirjam!!!

TCG member, Máire Ní Leathlobhair, recently returned from a field trip to Argentina. Máire's trip was funded by a Santander Mobility grant awarded by the University of Cambridge. In Argentina, she worked with vets and researchers based at the University of Buenos Aires (UBA) as well as the Catholic University of Córdoba (UCC), to collect samples and to study the prevalence of CTVT in Argentinian street dogs. We wish to say a huge thank you to Dr. María Verónica Brignone (UBA), Dr. César Koci, and Dr. Diego Graiff (UCC) as well as all of the fantastic veterinary hospital staff who helped with the sampling.

Many congratulations to Maximilian R. Stammnitz's new paper published on Cancer Cell, April 9, 2018!!

http://www.cell.com/cancer-cell/pdfExtended/S1535-6108(18)30117-X

Well done Max and everyone!!

BBC News

Tasmanian devil cancers targeted by human drugs

http://www.bbc.co.uk/news/uk-england-cambridgeshire-43698885

Cambridge University Research News

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

https://www.cam.ac.uk/research/news/human-anti-cancer-drugs-could-help-treat-transmissible-cancers-in-tasmanian-devils

Mr. Juan Carlos Ramirez Ante from University of Caldas, Colombia, came to visit TCG for two weeks in January 2018. Juan is a Veterinarian and currently doing his Master degree at Professor Francisco Pedraza's group at University of Caldas.  Professor Pedraza and Juan are collaborators of our ongoing CTVT projects and had sent us hundreds of CTVT samples in the past few years. He spent two weeks with TCG members learning experimental methods for the analysis of Canine transmissible venereal tumour (CTVT), and investigated the journey of CTVT tissue samples from the biopsy to genomic DNA sequencing. We will also further develop a joint project on CTVT chemotherapy response.

Elizabeth Murchison has been elected as part of the 2017 intake of the EMBO Young Investigator Programme for young European researchers in life sciences. 

Congratulations to Maximilian Stammnitz, who has won first prize for his poster “Disease doppelgängers: genomic characterisation of two transmissible cancers in Tasmanian devils” at the EMBL Cancer Genomics Conference in Heidelberg!

Many congratulations to Adrian Baez-Ortega, who won the 2017 Abcam Prize for Graduate Research at the Department of Veterinary Medicine! Adrian's research focuses on understanding the diversity and evolution of the canine transmissible venereal tumour.

TCG Part II student Alex Sampson won the Prize for best project in Part II Pathology (Cancer and Genetic Diseases) for his project "Characterising somatically arising nuclear insertions of mitochondrial DNA (NuMTs) in Canine Transmissible Venereal Tumour".

Many congratulations Alex!

Many congratulation on Máire Ní Leathlobhair’s new paper "No evidence for clonal transmission of urogenital carcinoma in California sea lions (Zalophus californianus)" published by Wellcome Open Research on the 22nd June 2017!

Well done Máire!

Many congratulations to Adrian Baez-Ortega and Kevin Gori on their new review, 'Computational approaches for discovery of mutational signatures in cancer' (BIB-17-0115.R1), which has been accepted for publication in Briefings in Bioinformatics on the 27th June 2017.

Well done both of you!

Congratulations to Andrea Strakova, who has been awarded the 2017 Canine Health Awards Postgraduate Student Inspiration Award from the Kennel Club. Andrea will receive £10,000, which she will use to support her postdoctoral research on CTVT. Find more information about the award here.

Andrea Strakova has been selected as one of twelve recipients of the 2017 Cambridge Society for the Application of Research (CSAR) student awards. The awards recognise excellence in research by postgraduate students at the University of Cambridge. Andrea’s research is on the evolution and host interactions of the canine transmissible venereal tumour. More information on the awards can be found here. Congratulations Andrea!

Several TCG members attended the 9th International Conference on Canine and Feline Genomics in Saint Paul, Minnesota. Congratulations to Adrian Baez-Ortega who won a Student Travel Award for best student abstract.

Dr. Rodrigo Hamede from the University of Tasmania, came to visit the TCG this week. Rodrigo is a colleague working on Tasmanian devils, we had a nice discussion about our current projects and future collaborations.  

TCG member Dr. Tracy Wang recently attended "The 6th China Small Animal Veterinary Physician Conference", which was held in Haikou, China, April 10-13, 2017. China Small Animal Veterinary Physician Conference has been recognized as the industry's most authoritative in mainland China,  it provides the best platform for the highest level of lecturers for practicing small animal vets continuing education, fantastic opportunities for Chinese and foreign small animal clinical technology exchange and international collaboration. Tracy has successfully set up the link between TCG group and small animal vets in China. We are looking forward for many more collaborations in the future.

The 2016 TCG Christmas Party! Merry Christmas everyone!