Cancer is generally considered a private disease which arises in an individual with inherited, spontaneous, or induced genetic changes that predispose to malignant transformation. However, there are rare examples of transmissible cancers in non-human species. It has been appreciated for 130 years that canine transmissible venereal tumor (CTVT) spreads among dogs through sexual and oral contact. Living histiocytic tumor cells pass from one individual to another and establish new tumors in the recipient. In this paper, Murgia and colleagues present evidence that cases of CTVT in diverse dog breeds and geographic locations are descendants of a single rogue tumor estimated to have arisen between 200 and 2500 years ago. The investigators took advantage of modern DNA analysis to show that tumors in 40 dogs on five continents over 20 years all had the same genetic signatures. Although the tumors could be assigned to two subclades, they appear to have arisen from the same ancestral tumor, which gave rise to the subclades early after its establishment as a transmissible malignant parasite. All carry a characteristic insertion of a LINE DNA repetitive element close to the c-myc proto-oncogene. They share other distinct genetic markers that distinguish the tumor from its hosts. The authors conclude that the CTVT cells represent the oldest mammalian cell line in continuous propagation – the widely used HeLa cell line is quite young by comparison.
In Brief
There are several important lessons to be learned from this study. First, the relative genomic stability of CTVT is surprising – although aneuploid, the karyotype is unexpectedly preserved. This may be relevant to its success as a parasitic tumor. CTVT regresses spontaneously and does not kill its hosts, suggesting that there is selective pressure on the tumor cells to maintain their immortality by ensuring that they can continue to be transmitted to others. However, the fact that the tumor cells must propagate asexually suggests that, over a long enough time, they will acquire deleterious mutations that will impair their viability. Second, the tumor has escaped from the normal allo-recognition mechanisms of its MHC-incompatible hosts. The authors raise the interesting notion that the highly polymorphic MHC system may have evolved to protect animals from transmissible tumors as well as infectious agents. But they point out that MHC antigens are suppressed by many types of tumors, raising the interesting questions of why transmissible allograft tumors have not emerged more frequently and why they have not (yet?) been observed in human populations.
Competing Interests
Dr. Andrews indicated no relevant conflicts of interest.
