Researchers reporting in the February 17th issue of the Cell Press journal Cell have sequenced the complete genome of one immortal devil. The genomes of the Tasmanian devil and its transmissible cancer may help to explain how that cancer went from a single individual to spreading through the population like wildfire.
The deadly transmissible facial cancer has led to the speedy decline of the island-dwelling Tasmanian devil population since its discovery and now threatens the entire species with extinction. Ultimately, the researchers hope that the new findings might point to a way to help save the Tasmanian devils.
"There are targeted drugs that work against cancer genes," said Elizabeth Murchison, a Tasmanian native working at the Wellcome Trust Sanger Institute in the United Kingdom. "We hope some of the mutations that we have found in genes in the devil cancer may point to therapeutic strategies."
Tasmanian facial cancer disease is spread from one Tasmanian devil to another through bites that transfer living cancer cells, and Tasmanian devils bite each other often. The first photograph of a Tasmanian devil with one of these facial tumors turned up in 1996. "At the time, it was thought to be a one-off case," Murchison said.
But soon, dozens more sick devils turned up, and by the early 2000s, "it was clear that this was a new type of infectious disease," she said. The real breakthrough came in 2006 when it was shown that all of the cancers were actually one, passed on clonally from one animal to another. That was a particular surprise because cancer doesn't usually hop from one individual to another, except in very rare instances. Normally, the immune system ensures that foreign cancers cannot survive in new hosts.
In search of answers and potential solutions, Murchison and her colleagues set out to sequence the Tasmanian devil genome and that of the cancer. Their analyses suggest that the cancer first arose relatively recently in a female Tasmanian devil.
"I call her the immortal devil," Murchison said. "Her cells are living on long after she died."
"The cancer genome has evolved as it has spread through the population, but overall it appears to be rather stable," adds Michael Stratton, senior author of the paper. "The genetic differences between 104 Tasmanian devil tumors from all around the island present us with a remarkably clear picture of how the cancer has spread in time and space over the last couple of decades, which may help with strategies for disease containment."
More than 17,000 mutations in the devil cancer genome have been catalogued, and while that may sound like a lot, it is comparable to the number of mutations found in some human cancers, says Murchison. The task now is to figure out which of the thousands of mutations are most important. Early indications suggest that changes in the immunity genes might ultimately explain how the cancer evades the immune system.
The world has already lost the Tasmanian tiger, which went extinct in the 1930s. "It would be really sad to lose our two largest marsupial carnivores, and within 100 years of each other," Murchison said. Hopefully, the new data will lead to some more definitive answers, and soon.
- 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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