comparison against 186 canid wholegenome sequences reveals survival strategies of an ancient clonally transmissible canine tumor 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 worlds oldest known continuously propagating somatic cell lineage we created the largest existing catalog of canine genomewide variation and compared it against two ctvt genome sequences thereby separating alleles derived from the founders genome from somatic mutations that must drive clonal transmissibility we show that ctvt has undergone continuous adaptation to its transmissible allograft niche with overlapping mutations at every step of immunosurveillance particularly selfantigen presentation and apoptosis we also identified chronologically early somatic mutations in oncogenesis and immunerelated genes that may represent key initiators of clonal transmissibility thus we provide the first insights into the specific genomic aberrations that underlie ctvts dogged perseverance in canids around the world