Transmissible Tumors: Breaking the Cancer Paradigm

Transmissible tumors are those that have transcended the bounds of their incipient hosts by evolving the ability to infect another individual through direct transfer of cancer cells, thus becoming parasitic cancer clones. Coitus, biting, and scratching are transfer mechanisms for the two primary species studied, the domestic dog (Canis lupus familiaris) and the Tasmanian devil (Sarcophilus harrisii). Canine transmissible venereal tumors (CTVT) are likely thousands of years old, and have successfully travelled from host to host around the world, while the Tasmanian devil facial tumor disease (DFTD) is much younger and geographically localized. The dog tumor is not necessarily lethal, while the devil tumor has driven the population to near extinction. Transmissible tumors are uniform in that they have complex immunologic profiles, which allow them to escape immune detection by their hosts, sometimes for long periods of time. In this review, we explore how transmissible tumors in CTVT, DFTD, and as well as the soft-shell clam and Syrian hamster, can advance studies of tumor biology.

TrendsRecent whole-genome sequencing (WGS) of CTVT has provided the first detailed glimpse into mechanisms allowing transmissibility.Evaluation of CTVT against 186 canine whole genomes drastically increased the ability to distinguish between somatic and germline variants, leading to accurate classification of single nucleotide variants (SNVs), insertions and deletions (indels), and structural variants (SVs).This evaluation, as well as a more accurate depiction of tumor evolution, has resulted in a better understanding of the underlying immunology that facilitates the characteristic transmissibility of transmissible tumors.DFTD shows evidence for convergent evolution with the much older CTVT within class I MHC molecule presentation, indicating an essential hurdle for host immune evasion.Additional transmissible tumor models in the Syrian hamster and soft-shell clam may further highlight commonalities and divergences between tumor transmissibility mechanisms.