Despite several BTN clones having been newly described in recent years, no analyses of whole BTN genomes have yet been reported. Combining a range of approaches, our study provides a first outlook into the genomes of these singular marine leukaemias in European common cockles, complementing the work of Hart et al. on American soft-shell clams. Both studies reveal neoplastic genomes marked by structural instability. In the case of cockle BTN, we find evidence for ongoing extreme genomic instability, most likely activated by early whole-genome duplication and fuelled by recurrent chromosome mis-segregation during mitosis. This is in stark contrast with the three transmissible cancers described in terrestrial mammals (dogs and Tasmanian devils), which present remarkable karyotypic stability, and thus challenges the notion that development of a durable genome architecture is required for long-term survival of cancer lineages. Although our data do not allow estimation of precise ages for cockle BTN, multiple lines of evidence suggest that these clones may have emerged centuries or millennia ago. These include the broad geographic distribution of tumours, the marked genetic divergence between tumours and modern cockles, the recurrent capture of host mitochondria by tumours, and the absence in tumours of satellite DNA elements that are vastly expanded in the cockle germ line. Furthermore, Hart et al. estimate an age of ~500 years for the BTN clone affecting soft-shell clams, supporting that long-term survival of marine transmissible cancers is possible. Taken together, our findings suggest that CedBTN lineages have undergone a relatively long history of pervasive genomic instability. Studying the mechanisms that enable BTN cells to overcome the effects of such instability will broaden our understanding of the conditions required for cancers to survive and adapt over the long term.
In adiition, the results of warty venus clams reveal the existence of a transmissible leukemia originated in a striped venus clam, most likely C. gallina, which was transmitted to a second species, the warty venus clam (V. verrucosa), and among whose specimens it currently propagates. We identified this parasitic cancer in warty venus clams from two sampling points that are more than 1,000 nautical miles away in the coasts of Spain, bathed by two different seas, the Atlantic Ocean and the Mediterranean Sea. The analysis of mitochondrial and nuclear gene sequences revealed no nucleotide diversity within the seven tumours sequenced, which supports that all belong to the same neoplastic lineage that spreads between Veneridae clams in the Seas of Southern Europe. Although we ignore the age of this cancer clone, we can confirm it arose before 2011, when the neoplastic warty venus specimen EVVV11-02 was collected. The apparent lack of genetic variation between all tumours, even from distant sampling points, suggests either that this cancer is very recent, or that it may have been unintentionally scattered by the action of man, a way of transmission that has been proposed for other bivalve transmissible cancers.
