Peer-reviewed veterinary case report
Genetic variants linked to blood cancers in retriever dogs
By Evans, Jacquelyn M et al.·Published in PLoS genetics·2021·National Human Genome Research Institute, United States·View original on PubMed →
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Original publication title: Multi-omics approach identifies germline regulatory variants associated with hematopoietic malignancies in retriever dog breeds.
- Species:
- dog
Plain-English summary
A flat-coated retriever was found to have a high risk of developing histiocytic sarcoma, a serious type of cancer that affects certain immune cells. Research showed that specific genetic factors on chromosomes 5 and 19 are linked to this cancer in flat-coated retrievers, with one gene potentially influencing the development of multiple types of blood cancers. Understanding these genetic markers can help identify dogs at risk and guide future treatments. While this study focused on genetic research, it highlights the importance of monitoring flat-coated retrievers for signs of cancer due to their increased susceptibility.
People also search for: flat-coated retriever cancer risk · histiocytic sarcoma in dogs · dog cancer genetic testing
Abstract
Histiocytic sarcoma is an aggressive hematopoietic malignancy of mature tissue histiocytes with a poorly understood etiology in humans. A histologically and clinically similar counterpart affects flat-coated retrievers (FCRs) at unusually high frequency, with 20% developing the lethal disease. The similar clinical presentation combined with the closed population structure of dogs, leading to high genetic homogeneity, makes dogs an excellent model for genetic studies of cancer susceptibility. To determine the genetic risk factors underlying histiocytic sarcoma in FCRs, we conducted multiple genome-wide association studies (GWASs), identifying two loci that confer significant risk on canine chromosomes (CFA) 5 (Pwald = 4.83x10-9) and 19 (Pwald = 2.25x10-7). We subsequently undertook a multi-omics approach that has been largely unexplored in the canine model to interrogate these regions, generating whole genome, transcriptome, and chromatin immunoprecipitation sequencing. These data highlight the PI3K pathway gene PIK3R6 on CFA5, and proximal candidate regulatory variants that are strongly associated with histiocytic sarcoma and predicted to impact transcription factor binding. The CFA5 association colocalizes with susceptibility loci for two hematopoietic malignancies, hemangiosarcoma and B-cell lymphoma, in the closely related golden retriever breed, revealing the risk contribution this single locus makes to multiple hematological cancers. By comparison, the CFA19 locus is unique to the FCR and harbors risk alleles associated with upregulation of TNFAIP6, which itself affects cell migration and metastasis. Together, these loci explain ~35% of disease risk, an exceptionally high value that demonstrates the advantages of domestic dogs for complex trait mapping and genetic studies of cancer susceptibility.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/33983928/