Evidence for a genetic basis of urogenital carcinoma in the wild California sea lion

Helen M. Browning, Karina Acevedo-Whitehouse, Frances M. D. Gulland, Ailsa J. Hall, Jeanie Finlayson, Mark P. Dagleish, Karen J. Billington, Kathleen Colegrove, John A. Hammond

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Although neoplasia is a major cause of mortality in humans and domestic animals, it has rarely been described in wildlife species. One of the fewexamples
is a highly prevalent urogenital carcinoma in California sea lions (CSLs).
Although the aetiology of this carcinoma is clearly multifactorial, inbreeding
depression, as estimated using levels of microsatellite multilocus heterozygosity,
is identified as predictive for this neoplasia. On further analysis, this
relationship appears to be largely driven by one marker, suggesting that a
single locus might be associated with the occurrence of this disease in CSLs.
In a case–control study, carcinoma was significantly associated with homozygosity at the Pv11 microsatellite locus. Pv11 was mapped to intron 9 of
the heparanase 2 gene (HPSE2) locus, a very large gene encoding heparanase
2, which in humans is associated with multiple carcinomas. Correspondingly,
immunohistochemical labelling in tissues was present in carcinoma cases
within a single homozygous Pv11 genotype. To our knowledge, this is the
first report of an individual locus being associated with cancer in any wildlife
species. This adds emphasis to the study of HPSE2 in other species, including
humans and will guide future studies on this sentinel species that shares much
of its diet and environment with humans

Original languageEnglish
Article number20140240
Number of pages10
JournalProceedings of the Royal Society B: Biological Sciences
Issue number1796
Early online date22 Oct 2014
Publication statusPublished - Dec 2014


  • Cancer
  • Heparanase 2 gene
  • Wildlife
  • Odds ratio


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