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Cancer genetics

The origin and evolution of an ancient cancer

Nature Reviews Genetics volume 15, page 144 (2014)Cite this article

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Murchison et al. sequenced the genomes of two CTVT tumours and their hosts, located in Brazil and Australia. Despite massive karyotype abnormalities, the tumour genomes were found by copy number analysis to be mostly diploid. This indicates that these structural aberrations in karyotype are generally copy number neutral. Interestingly, unlike human cancers, the authors observed no subclonality in the tumours, suggesting that CTVT is fairly genomically stable, and this may indicate that it is well adapted to its niche. Moreover, at least 646 genes, which represent 2.8% of total protein-coding genes in the dog genome, were found to be lost by deletion or nonsense mutation, and are thus collectively dispensable for cell survival.

The authors also identified four mutational signatures in CTVT, which explained 98% of all mutations in the CTVT genome. Three of these signatures are also found in human cancers: one is correlated with patient age, one has an unknown aetiology and one corresponds to exposure to ultraviolet (UV) radiation. Forty-two percent of mutations in CTVT are associated with this latter signature, indicating that the CTVT cancer cells have been periodically exposed to UV light during the history of the CTVT lineage.

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References

  1. Murchison, E. P. et al. Transmissible dog cancer genome reveals the origin and history of an ancient cell lineage. Science 343, 437–440 (2014)

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  1. Isabel Lokody
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Lokody, I. The origin and evolution of an ancient cancer. Nat Rev Genet 15, 144 (2014). https://doi.org/10.1038/nrg3676

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