Researchers have sequenced the genome of a contagious cancer that is threatening the Tasmanian devil, the world's largest carnivorous marsupial, with extinction. Cataloguing the mutations present in the cancer has led to clues about where the cancer came from and how it became contagious.
The research has revealed that the cancer, which is spread between animals by biting, first arose from the cells of a single female Tasmanian devil. This animal is nicknamed 'The Immortal Devil' because although she died more than 15 years ago, her DNA is living on in the contagious cancer cell line that she spawned. The cancer causes the appearance of tumours on the face of affected devils which grow rapidly and cause death within months.
"The Tasmanian devil cancer is the only cancer that is threatening an entire species with extinction," says Dr Elizabeth Murchison, lead author from the Wellcome Trust Sanger Institute. "Sequencing the genome of this cancer has allowed us to catalogue the mutations that caused this cancer to arise and to persist in the Tasmanian devil population."
The team found evidence for genetic differences between tumours, indicating that the cancer has genetically diverged during its spread through the Tasmanian devil population. They searched for these genetic differences between the tumours of 69 different devils from distant locations in Tasmania, allowing them to build up a map of the cancer's spread through the devil population. This indicates that some cancer sub-types may be more virulent than others.
"We found that devil cancer's genome has about 20,000 mutations. This is fewer mutations than are found in some human cancers and indicates that cancers do not need to be extremely unstable in order to become contagious." says Dr David Bentley, senior co-author from Illumina Cambridge Ltd. "Tracing the evolutionary history and spread of this cancer helps us to understand not only what caused this disease but also to predict how it might behave in the future."
The spread of cancer between individuals is normally prevented by the immune system, which can normally detect foreign tissues as 'non-self'. The team found some intriguing clues as to how the devil cancer may outwit the immune system, including mutations in a set of genes involved in immunity. However, future studies will be required to elucidate how cancer escapes the immune destruction.
"This research is important because it allows us to understand the pattern of disease spread and this may help contain the epidemic. However, we also now need to use the genome sequence to understand more about how this cancer became transmissible. Cancers that transmit through populations are obviously incredibly rare, but we should use the Tasmanian devil example to understand the process to be prepared in the extremely unlikely event that such an epidemic ever occurs in humans." says Professor Mike Stratton, senior author and Director of the Wellcome Trust Sanger Institute.
The next stage of the research will be to map the genomes of thousands of devil tumours in order to understand the genetic diversity present in the cancer and to investigate the genetic interactions between the cancer and the Tasmanian devil population.
- Elizabeth P. Murchison, Ole B. Schulz-Trieglaff, Zemin Ning, Ludmil B. Alexandrov, Markus J. Bauer, Beiyuan Fu, Matthew Hims, Zhihao Ding, Sergii Ivakhno, Caitlin Stewart, Bee Ling Ng, Wendy Wong, Bronwen Aken, Simon White, Amber Alsop, Jennifer Becq, Graham R. Bignell, R. Keira Cheetham, William Cheng, Thomas R. Connor, Anthony J. Cox, Zhi-Ping Feng, Yong Gu, Russell J. Grocock, Simon R. Harris, Irina Khrebtukova, Zoya Kingsbury, Mark Kowarsky, Alexandre Kreiss, Shujun Luo, John Marshall, David J. McBride, Lisa Murray, Anne-Maree Pearse, Keiran Raine, Isabelle Rasolonjatovo, Richard Shaw, Philip Tedder, Carolyn Tregidgo, Albert J. Vilella, David C. Wedge, Gregory M. Woods, Niall Gormley, Sean Humphray, Gary Schroth, Geoffrey Smith, Kevin Hall, Stephen M.J. Searle, Nigel P. Carter, Anthony T. Papenfuss, P. Andrew Futreal, Peter J. Campbell, Fengtang Yang, David R. Bentley, Dirk J. Evers, Michael R. Stratton. Genome Sequencing and Analysis of the Tasmanian Devil and Its Transmissible Cancer. Cell, 2012; 148 (4): 780 DOI: 10.1016/j.cell.2011.11.065
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