Canine transmissible venereal tumour (CTVT) is a cancer that spreads between dogs through the transfer of living cancer cells, primarily during mating. This leads to the formation of genital tumours in both male and female dogs.
This unusual cancer arose from the cells of one individual dog living around 8,000 years ago, but survived beyond the death of the original dog by spreading to new dogs.
The contagious cancer is now found in dog populations worldwide, and is the oldest and most prolific cancer lineage known in nature.
Mitochondria are structures within animal cells that produce energy. They contain their own genetic material – known as mitochondrial DNA – that is different from the DNA found in the cell’s nucleus.
Previous work on CTVT has revealed the surprising discovery that mitochondrial DNA transfers between the tumour and host. Further work, from the Transmissible Cancer Group based at the University of Cambridge’s Vet School, went on to show that mitochondrial DNA from the tumour and host sometimes mixes.
Researchers found that mitochondrial DNA molecules from host cells that have migrated into tumour cells occasionally fuse with the tumour’s own mitochondrial DNA, sharing host and tumour DNA in a process known as ‘recombination’.
This is the first time this process has been observed in cancers, and could aid the survival of this long-lived cancer lineage.
The capture of mitochondrial DNA (mtDNA) by CTVT creates a unique opportunity to understand the competitive dynamics of two types of mtDNA that come together within the same cell.
In a new study, published in Nature Communications in June 2020, the authors show that one particular type of mtDNA – named A1d1a – has been recurrently captured by CTVT cancer cells on eleven independent occasions.
A1d1a is highly over-represented for CTVT mitochondrial capture compared with its frequency in the dog population.
The authors propose that A1d1a mitochondria unexpectedly have a ‘selfish’ replicative advantage – by replicating more efficiently – rather than by providing a functional advantage.
Apart from providing insights into the characteristics enabling the spread of this canine cancer that has ‘metastasised’ on a global scale, this work is of much broader importance, as understanding the competitive dynamics of mtDNA is crucial for advancing knowledge of mtDNA genetic diseases and assessing the risks of therapeutic mtDNA transplantation in human embryos.
Reference
Strakova, A., Nicholls, T.J., Baez-Ortega, A. et al. Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer. Nat Commun 11, 3059 (2020). https://doi.org/10.1038/s41467-020-16765-w
