Résumé
SignificanceCancer is usually considered to be a clonal entity, meaning that cells of a cancer are believed to be direct genetic descendants of the original transformed cancer cell. It is possible, however, that cancer cells could acquire DNA from normal cells through a process known as horizontal gene transfer. Exploiting the unusual genetic features of transmissible cancers, long-lived cancers that spread between animals by transfer of living cancer cells, we demonstrate that a dog transmissible cancer has taken up and incorporated a large piece of DNA by horizontal transfer. This may have occurred through engulfment of fragments of a dying cell. Cancer is therefore not always entirely clonal, and horizontal gene transfer provides a previously overlooked mechanism of genome diversification.
Horizontal transfer of nuclear DNA between cells of host and cancer is a potential source of adaptive variation in cancer cells. An understanding of the frequency and significance of this process in naturally occurring tumors is, however, lacking. We screened for this phenomenon in the transmissible cancers of dogs and Tasmanian devils and found an instance in the canine transmissible venereal tumor (CTVT). This involved introduction of a 15-megabase dicentric genetic element, composed of 11 fragments of six chromosomes, to a CTVT sublineage occurring in Asia around 2,000 y ago. The element forms the short arm of a small submetacentric chromosome and derives from a dog with ancestry associated with the ancient Middle East. The introduced DNA fragment is transcriptionally active and has adopted the expression profile of CTVT. Its features suggest that it may derive from an engulfed apoptotic body. Our findings indicate that nuclear horizontal gene transfer, although likely a rare event in tumor evolution, provides a viable mechanism for the acquisition of genetic material in naturally occurring cancer genomes.