07:37pm Monday 11 December 2017

Fatal devil cancer genome sequenced

An international team of scientists has worked to piece together the genome of a fatal cancer that is sweeping through Tasmanian devils. Their work, published in ‘Cell’, gives important clues to how the tumour evades detection by the devils’ immune system and shows – for the first time – that the devil in which the tumour originated was a female.

Tasmanian devil facial tumour disease is one of only two naturally occurring transmissible cancers known (the other affects dogs). Transmissible cancers pass between animals by the physical transfer of cancer cells. The devil disease, which causes tumours to the head and face, is fatal, usually within six to nine months of the onset of symptoms.

Because the cancer is spread by the physical exchange of cancer cells, all tumours killing devils today are descended from the same single cancer, originating in a single devil. To assemble the cancer genome of this so-called ‘immortal devil’, the researchers sequenced the genomes of a healthy male and female devil and the genomes of tumours taken from two devils from the north and south of Tasmania.

By comparing the cancer genomes with the normal genomes, they were able to work out which mutations arose as the cancer developed and which were normal genetic variants present in the genome of the original devil.

They found more than 17 000 genetic mutations in the cancer genome – fewer than expected. “Our findings indicate that it’s a relatively stable cancer, one whose genome has remained fairly intact in spite of the fact that it’s transmissible and it has passed through a number of individuals,” says Dr Elizabeth Murchison, lead author on the paper. “This shows that a cancer does not need to have an incredibly unstable genome in order to become transmissible.”

The researchers identified 458 genes with mutations that change the coding regions (the parts that contain the instructions to make proteins), including mutations in two genes that are frequently mutated in human cancers. The researchers are now planning to build on this work and explore further how this cancer evades detection by the devil immune system.

“We still don’t know how the cancer is able to spread without eliciting an immune response,” says Elizabeth. “We’d like to understand this more, ultimately so that we can work to develop vaccines and therapies that could help with conservation.”

“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.

This paper also contains the first evidence for natural selection operating on the cancer. When the team compared the genetic profiles of 104 devil tumours from across Tasmania, they found that the cancer had diverged into several genetically distinct subtypes during its spread across the island. On an isolated peninsula on the south-east coast, however, they found that one type of tumour had become progressively more dominant, suggesting that it had acquired a selective advantage.

Tasmanian devil facial tumour disease was first seen on the island of Tasmania in 1996 and has spread widely since. As a result, the Tasmanian devil is at risk of extinction, and is on the red list of the International Union for the Conservation of Nature and Natural Resources.

For more information, read our feature articles on Elizabeth Murchison’s work and on transmissible cancers.

Image: Tasmanian devil. Credit: Ian D Williams, Anaspides Photography.

Reference

Murchison EP et al. Genome sequencing and analysis of the Tasmanian devil and its transmissible cancer. Cell 2012;148:780-91.

Wellcome Trust, Gibbs Building, 215 Euston Road, London NW1 2BE, UK T:+44 (0)20 7611 8888

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