Whole genome sequences of two canine transmissible venereal tumours (CTVTs) and their hosts derived from Australia and Brazil

Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell lineage. It is a transmissible cancer that propagates naturally in dogs. We sequenced the genomes of two CTVT tumors and found that CTVT has acquired 1.9 million somatic substitution mutations and bears evidence of exposure to ultraviolet light. CTVT is remarkably stable and lacks subclonal heterogeneity despite thousands of rearrangements, copy number changes and retrotransposon insertions. More than 10,000 genes carry non-synonymous variants and 646 genes have been lost. CTVT first arose in a dog with low genomic heterozygosity that may have lived approximately 11,000 years ago. The cancer spawned by this individual dispersed across continents approximately 500 years ago. Our results provide a genetic identikit of an ancient dog and demonstrate the robustness of mammalian somatic cells to survive for millennia despite a massive mutation burden.