Under the Radar: Survival Strategies of an Ancient Clonally Transmissible Canine Tumor. RO2-Rottweiler

Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world’s oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder’s genome from somatic drivers of clonal transmissibility. We show that CTVT is exquisitely adapted to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly MHC Class I antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis and immune-related genes that likely represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT’s dogged perseverance in canids around the world.