Devil facial tumour disease

Devil facial tumour disease (DFTD) is an aggressive non-viral clonally transmissible cancer which affects Tasmanian devils, a marsupial native to Australia. DFTD was first described in 1996. In the subsequent decade the disease ravaged Tasmania's wild devils. Affected high-density populations suffered up to 100% mortality in 12–18 months. Between 1996 and 2015, the population dwindled by 95%. Devil facial tumour disease (DFTD) is an aggressive non-viral clonally transmissible cancer which affects Tasmanian devils, a marsupial native to Australia. DFTD was first described in 1996. In the subsequent decade the disease ravaged Tasmania's wild devils. Affected high-density populations suffered up to 100% mortality in 12–18 months. Between 1996 and 2015, the population dwindled by 95%. There is often more than one primary tumour. Visible signs of DFTD begin with lumps of soft tissue around the mouth, which ulcerate. Tumours are locally aggressive, destroying the underlying bone of the jaw which interferes with feeding. Tumours may also cover the eyes. Devils usually die within six months from organ failure, secondary infection, or metabolic starvation. DFTD is rare in juveniles. DFTD affects males and females equally. The most plausible route of transmission is through biting, particularly when canine teeth come into direct contact with the diseased cells. Other modes of transmission may include the ingestion of infected carcasses and the sharing of food, both of which involve an allogeneic transfer of cells between unrelated individuals. The animals most likely to become infected are the fittest devil individuals. DFTD tumours are large soft tissue masses which become centrally ulcerated. The tumours are composed of lobules of nodules of round to spindle-shaped cells, often within a pseudocapsule. Tumours metastasise to regional lymph nodes involvement and systemically to the lungs, spleen and heart. Tasmanian devil cells have 14 chromosomes; the oldest-known strain of the tumour cells have thirteen chromosomes, nine of which are recognisable and four of which are mutated 'marker' chromosomes. More recently evolved strains have an additional mutant marker chromosome, for a total of fourteen chromosomes. Researchers identified the cancer as a neuroendocrine tumour, and found identical chromosomal rearrangements in all the cancer cells. The karyotype anomalies of DFTD cells are similar to those of cancer cells from canine transmissible venereal tumour (CTVT), a cancer of dogs that is transmitted by physical contact. Among the mutations present in the tumour genome is trisomy in chromosome 5p, as well as several single base mutations, and short insertions and deletions, e.g., deletions in the chromosomes 1, 2 and 3. Some of the mutated or deleted genes in DFTD are RET, FANCD2, MAST3 and BTNL9-like gene. Classical DFTD likely originated in the Schwann cells of a single devil. Schwann cells are found in the peripheral nervous system, and produce myelin and other proteins essential for the functions of nerve cells in the peripheral nervous system. Researchers sampled 25 tumours and found that the tumours were genetically identical. Using deep sequencing technology, the study authors then profiled the tumours' transcriptome, the set of genes that are active in tumours; the transcriptomes closely matched those of Schwann cells, revealing high activity in many of the genes coding for myelin basic protein production. Several specific markers were identified, including the MBP and PRX genes, which may enable veterinarians to more easily distinguish DFTD from other types of cancer, and may eventually help identify a genetic pathway that can be targeted to treat it. In 2015, a second genetically distinct strain of DFTD was identified, which was tetraploid, not diploid like the main form of the cancer. The tetraploid form has been linked to lower mortality rates. The cell type origin of this strain of DFTD is unknown. Increased levels of tetraploidy have been shown to exist in the oldest strain of DFTD as of 2014, which correlates with the point at which devils became involved in a DFTD removal programme. Because ploidy slows the tumour growth rate, the DFTD removal programme has been suggested as a selective pressure favouring slower-growing tumours, and more generally that disease eradication programmes aimed at DFTD may encourage the evolution of DFTD. The existence of multiple strains may complicate attempts to develop a vaccine, and there are reports of concerns that the evolution of the cancer may allow it to spread to related species such as the quoll. Wild Tasmanian devil populations are being monitored to track the spread of the disease and to identify changes in disease prevalence. Field monitoring involves trapping devils within a defined area to check for the presence of the disease and determine the number of affected animals. The same area is visited repeatedly to characterise the spread of the disease over time. So far, it has been established that the short-term effects of the disease in an area can be severe. Long-term monitoring at replicated sites will be essential to assess whether these effects remain, or whether populations can recover. Field workers are also testing the effectiveness of disease suppression by trapping and removing diseased devils, with the expectation that removal of diseased devils from wild populations would decrease disease prevalence, allowing devils to survive beyond juvenile years and so to breed. One study reported that a system of culling prior to 2010 did not impede disease spread.