Devil Facial Tumor Disease Has The Potential To Provide Insight Into Human Cancers

The emergence of a fatal transmissible cancer, devil facial tumor disease (DFTD) is threatening the iconic Tasmanian devil with extinction in the wild. Tumor cells are transmitted as an allograft by biting, where they escape immune detection by a currently unknown mechanism. Genomic technologies are allowing rapid progress to be made in understanding this disease. Genome and transcriptome sequencing, and molecular cytogentic analysis of DFTD tumors suggests that the tumor arose from a Schwann cell in a female devil over 15 years ago. The extensive rearrangement of limited regions of the genome suggests that DFTD may have arisen from a chromothripsis event, where these regions were shattered and rejoined to form the distinctive DFTD marker chromosomes. Interestingly, these regions are not only extensively rearranged in DFTD but are also highly rearranged between different marsupial species, suggesting a potential link between tumor and evolutionary breakpoints. Cells from that original tumor have since passaged through at least 100,000 individuals, evolving along the way. Interestingly, DFTD evolution by structural mutations is seemingly restricted to well demarcated regions of the genome, predominantly those regions consisting of chromosome 4, 5 and X material. The generally stable nature of DFTD chromosomes contrasts the chromosome instability observed for many solid tumors in humans. As a relatively stable tumor cell line, DFTD provides a unique opportunity to gain insight into the factors affecting genome instability, the link between evolutionary and tumor breakpoints and immune evasion in human cancers.