Whole genome sequences of two canine transmissible venereal tumours (CTVTs) and their hosts derived from Australia and Brazil. Transmissible dog cancer genome reveals the origin and history of an ancient cell lineage

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.

犬传染性生殖道肿瘤（Canine transmissible venereal tumor, CTVT）是已知最古老的体细胞谱系。它是一种可在犬类中自然传播的传染性肿瘤。我们对两株CTVT肿瘤的基因组进行了测序，发现该肿瘤累计携带190万个体细胞替换突变，且存在曾暴露于紫外线辐射的遗传证据。尽管存在数千次染色体重排、拷贝数变异以及反转录转座子插入事件，CTVT仍表现出极高的基因组稳定性，且不存在亚克隆异质性。超过10000个基因携带非同义变异，另有646个基因发生了缺失。CTVT最初起源于一只基因组杂合度较低的犬只，该个体大约生活在11000年前。由该个体衍生的肿瘤细胞系在约500年前扩散至各大洲。本研究结果不仅勾勒出一只古代犬只的遗传特征画像，同时证实了哺乳动物体细胞即便承载海量突变负荷，仍可存活数千年的极强鲁棒性。