Cross-species exome sequencing reveals recurrent genomic alterations in California sea lion (Zalophus californianus) urogenital carcinoma and highlights a recurrent PD-L1 variant
- Cancer
- Climate change
Abstract
Human-driven environmental change can promote cancer development in wild species, yet the pathophysiology of wildlife cancers remain largely unexplored. Urogenital carcinoma (UGC) in the California sea lion (CSL) (Zalophus californianus) is one of the most common cancer types documented in any wild mammal. The pathogenesis of UGC in CSLs is known to be multifactorial, with links to environmental contaminant exposure and infection by Otarine Herpesvirus-1 (OtHV-1); however, the genomic features of these cancers have not been thoroughly explored. Understanding UGC pathogenesis in the CSL has important implications for the health of humans and other species that share environment and diet. Methods: We leveraged the evolutionary conservation between the domestic dog and CSL genomes to perform cross-species whole-exome sequencing (WES) of CSL UGC tumors and matched normal tissue pairs. We also used PCR and Sanger sequencing to investigate the prevalence of DNA from OtHV-1. Results: Bioinformatic analyses identified shared somatic variants and DNA copy number aberrations in UGC tumor samples, including recurrent exonic single-nucleotide variants in CD274/PD-L1, and recurrent copy number gains in CD274/PD-L1, TNFRSF14, CD200, CDK4, and PLCG2. In an extended cohort of 70 CSLs (tumor, matched normals, and controls), a recurrent C > T single-nucleotide variant in exon 4 of CD274/PD-L1 was identified in 54 of 68 (79.4%) CSLs with diagnosed UGC. OtHV-1 DNA was detected in 67 of 70 individuals (95.8%). Conclusions: These results demonstrate that cross-species exome capture provides a means to identify genomic alterations that may play a role in the molecular pathogenesis of UGC in the CSL and adds to the body of evidence for an association between OtHV-1 and UGC in this species.
Livingston, I. G., Wise, C. F., Dickey, A. N., Thomas, R., Deming, A. C., Halaska, B., Gulland, F. M. D., Colegrove, K. M., Duignan, P., & Breen, M. (2026). Cross-species exome sequencing reveals recurrent genomic alterations in California sea lion (Zalophus californianus) urogenital carcinoma and highlights a recurrent PD-L1 variant. Genes, 17(2), 222. https://doi.org/10.3390/genes17020222
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{"image":"\/People\/Portrait\/cropped-images\/PD_Gray whale Pacifica_IMG_0552-0-0-1270-992-1775170630.jpeg","alt":"Padraig Duignan","title":"P\u00e1draig Duignan","text":"Senior Director, Research Pathology","link_url":"https:\/\/www.marinemammalcenter.org\/person\/padraig-duignan","link_text":"Read Bio"}
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