Hello,

My co-authors and I are excited to share our new research article exploring
the genomic signatures of Urogenital Carcinoma in the California sea lion.

This research uses cancer in California sea lions as a powerful comparative
model to understand how tumors arise and evade the immune system across
mammals. By identifying genomic changes shared between sea lion cancers and
human cancers, the study provides insight into immune-related pathways that
may inform future cancer immunotherapies and earlier diagnostic approaches.
At the same time, the work underscores the role of wildlife as sentinels of
environmental health, showing how studying naturally occurring cancers in
wild species can benefit both conservation efforts and human medicine.

Livingston, I.G.; Wise, C.F.; Dickey, A.N.; Thomas, R.; Demming, A.C.;
Halaska, B.; Gulland, F.M.D.; Colegrove, K.M.; Duignan, P.; Breen, M.
Cross-Species Exome Sequencing Reveals Recurrent Genomic Alterations in
California Sea Lion (*Zalophus californianus*) Urogenital Carcinoma and
Highlights a Recurrent PD-L1 Variant. *Genes* 2026, *17*, 222.
https://doi.org/10.3390/genes17020222

Abstract: Background/Objectives: 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.

Link to paper: https://www.mdpi.com/2073-4425/17/2/222

Cheers,
Isabella Livingston | she/her/hers
Genetics and Genomics Ph.D.Candidate
Genetics and Genomics Scholar
GAANN Biotechnology Fellow
Dept. of Molecular Biomedical Sciences, College of Veterinary Medicine
North Carolina State University
Raleigh, NC 27695
breenlab.org
_______________________________________________
MARMAM mailing list
[email protected]
https://lists.uvic.ca/mailman/listinfo/marmam

Reply via email to