An international team of scientists has found that cells that protect nerves are likely to be the origins of a fatal cancer known as Devil Facial Tumour Disease (DFTD) that is spreading rapidly through populations of Tasmanian devils in Australia: if unchecked, scientists estimate the cancer, which is spread through biting, could wipe out the wild devil population within the next 30 years or so.
The findings are the subject of a collaborative study led by Australian scientists that was published in the international journal Science on 1 January.
Devil Facial Tumour Disease (DFTD) is a transmissible cancer that affects only the Tasmanian devil, a carnivorous marsupial about the size of a small dog that is found in Australia and Tasmania. The disease causes large tumours that occur mostly on the face and mouth but also spreads to internal organs.
First reported in 1996, DFTD spreads by biting and quickly kills infected animals; so much so, they are now considered an endangered species facing extinction.
In this study, the researchers traced the origins of DFTD to a type of cell that protects peripheral nerve fibres, the Schwann cell. They extracted genetic data from biopsies of Tasmanian devil tumours and identified a genetic marker that could be used to diagnose DFTD.
Dr Elizabeth Murchison led the study when she was at the Cold Spring Harbor Laboratory, New York, and at the Australian National University in Canberra. She told the media that pinpointing the Schwann cell as the origin of the disease was an important discovery because there are no diagnostic tests, treatments or vaccines for DFTD.
Dr Tony Papenfuss, a geneticist at Melbourne’s Walter and Eliza Hall Institute, led the part of the study that discovered which genes were switched on in the tumours and identified their genetic signature:
“When we compared the signature of the tumours to other normal tissues we found the tumours were most like Schwann cells,” he told the press.
Murchison, Papenfuss and colleagues pinpointed networks of genes that may be important in the development and transmission of tumours. They also found that the tumours strongly express a gene for myelin basic protein, which is an important constituent of the sheaths that protect nerve fibres.
Out of the 20 tumour-specific genes they identified, they found that 9 played a role in myelination. They also discovered that DFTD tumours, and cells that had spread to other organs, tested positive for periaxin, a Schwann-cell protein, and other types of tumour did not test positive for this protein, suggesting it would make a reliable diagnostic marker for DFTD.
“Devils develop tumours of all different types and the genetic markers we have identified are useful for telling apart the tumours that occur in DFTD from other kinds of tumours,” said co-author Dr Greg Woods, Associate Professor at the University of Tasmania’s Menzies Research Institute.
Papenfuss explained that:
“Differentiating between the devil facial tumour disease and some other tumour is particularly important, especially when it comes to the insurance population programme.”
The insurance programme is a captive population of less than 200 uninfected Tasmanian devils held at zoos and parks in Tasmania and mainland Australia; conservationists aim to increase that population to at least 500.
Tamara Keeley, a reproductive biologist at the Taronga Western Plains Zoo in Dubbo in New South Wales, Australia, and not a co-author of the study, said that the biggest problem for conservationists was the absence of a test for DFTD. Currently, to prevent spread in the wild, conservation workers kill devils that show signs of the disease, but many infected animals can go undetected.
“If we had a blood test, we could remove disease carriers in the hopes of managing the wild population,” said Keeley.
Although the insurance programme has not captured wild Tasmanian devils since 2008, a diagnostic test would help with future efforts, she explained.
The study also suggested clues for how DFTD may dodge the immune system. Co-author Dr Alexandre Kreiss, from the University of Tasmania’s Menzies Research Institute in Hobart, where he is working on a vaccination programme, said Tasmanian devils are genetically very similar to each other, and it could be that the cancer cells from another devil are not recognized as foreign when they enter a new host.
On the other hand, it could be because the origin is in the peripheral nervous system, which is rarely targeted by the immune system, said Kreiss, and it might explain why experiments with irradiated cancer cells at the Menzies Research Institute have been disappointing. He explained to Nature News that only one out of six devils mounted an immune response in a recent vaccination trial.
Papenfuss said that although a vaccine against DFTD was still a long way off, we now have “a good start on a set of genomic tools we can move forward with”.
Dr Vanessa Hayes, a geneticist at the Children’s Cancer Institute Australia in Sydney, was not involved in the study, but she and her team are sequencing the genomes of Tasmanian devils to find gene variants that may confer resistance to DFTD. She told Nature News that this study was “very complementary” to the work they were doing.
The study is part of the Save the Tasmanian Devil Program and was sponsored by the National Health and Medical Research Council and the University of Tasmania’s Dr Eric Guiler Tasmanian Devil Research Grant.
“The Tasmanian Devil Transcriptome Reveals Schwann Cell Origins of a Clonally Transmissible Cancer.”
Elizabeth P. Murchison, Cesar Tovar, Arthur Hsu, Hannah S. Bender, Pouya Kheradpour, Clare A. Rebbeck, David Obendorf, Carly Conlan, Melanie Bahlo, Catherine A. Blizzard, Stephen Pyecroft, Alexandre Kreiss, Manolis Kellis, Alexander Stark, Timothy T. Harkins, Jennifer A. Marshall Graves, Gregory M. Woods, Gregory J. Hannon, and Anthony T. Papenfuss.
DOI: 10.1126/science.1180616
Source: Nature News, Walter and Eliza Hall Institute of Medical Research.
Written by: Catharine Paddock, PhD