ArticleGenome biology2013
Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B.
Article in Genome biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed.
- Berberine Chloride Suppresses Growth of Canine Osteosarcoma Cells via Regulating MMP2/AKT/β-Catenin Pathway.Antioxidants (Basel, Switzerland) · 2026Article
- Comparative Cancer Genetics and Veterinary Therapeutics in Dogs and Cats: A Species-Aware Framework for Comparative Oncology.Life (Basel, Switzerland) · 2026Review
- Cancer Across Domestic Animals: A Descriptive Review from the Veterinarian's Perspective.Veterinary sciences · 2026Review
- Genome Selection for Fleece Traits in Inner Mongolia Cashmere Goats Based on GWAS Prior Marker Information.Animals : an open access journal from MDPI · 2025Article
- Comparative Genetics of Canine and Human Cancers.Veterinary sciences · 2025Review
- Heterozygosity-Rich Regions in Canine Genome: Can They Serve as Indicators of Balancing Selection?Animals : an open access journal from MDPI · 2025Article
- Genetic variation near GRB10 associated with bone growth and osteosarcoma risk in canine and human populations.Cancer epidemiology · 2024Article
- Bringing the Genomic Revolution to Comparative Oncology: Human and Dog Cancers.Annual review of biomedical data science · 2024Review
- Clinical Use of Molecular Biomarkers in Canine and Feline Oncology: Current and Future.Veterinary sciences · 2024Review
- Clinical, pathologic and molecular findings in 2 Rottweiler littermates with appendicular osteosarcoma.Research square · 2024Article
- Article
- Identification of SNP markers for canine mammary gland tumours in females based on a genome-wide association study - preliminary results.Journal of veterinary research · 2023Article
- Genomic Medicine in Canine Periodontal Disease: A Systematic Review.Animals : an open access journal from MDPI · 2023Review
- Genomic analysis and prediction of genomic values for distichiasis in Staffordshire bull terriers.Canine medicine and genetics · 2023Article
- Sarcoma Predisposition in Dogs with a Comparative View to Human Orthologous Disease.Veterinary sciences · 2023Review
- Dog breeds and conformations predisposed to osteosarcoma in the UK: a VetCompass study.Canine medicine and genetics · 2023Article
- Article
- Genomic analysis of firework fear and noise reactivity in standard poodles.Canine medicine and genetics · 2023Article
- Risk factors for appendicular osteosarcoma occurrence in large and giant breed dogs in western Canada.The Canadian veterinary journal = La revue veterinaire canadienne · 2023Article
- Evaluating the Histologic Grade of Digital Squamous Cell Carcinomas in Dogs and Copy Number Variation of KIT Ligand-A Correlation Study.Veterinary sciences · 2023Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors.
Funding
Abstract
backgroundCanine osteosarcoma is clinically nearly identical to the human disease, but is common and highly heritable, making genetic dissection feasible.
resultsThrough genome-wide association analyses in three breeds (greyhounds, Rottweilers, and Irish wolfhounds), we identify 33 inherited risk loci explaining 55% to 85% of phenotype variance in each breed. The greyhound locus exhibiting the strongest association, located 150 kilobases upstream of the genes CDKN2A/B, is also the most rearranged locus in canine osteosarcoma tumors. The top germline candidate variant is found at a >90% frequency in Rottweilers and Irish wolfhounds, and alters an evolutionarily constrained element that we show has strong enhancer activity in human osteosarcoma cells. In all three breeds, osteosarcoma-associated loci and regions of reduced heterozygosity are enriched for genes in pathways connected to bone differentiation and growth. Several pathways, including one of genes regulated by miR124, are also enriched for somatic copy-number changes in tumors.
conclusionsMapping a complex cancer in multiple dog breeds reveals a polygenic spectrum of germline risk factors pointing to specific pathways as drivers of disease.
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