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Genomic study finds variants linked to cancer in Bernese Mountain Dogs, Rottweilers and Retrievers.
Six genetic variants add up to determine the risk of several blood cancers in predisposed dogs, according to a study by Benoît Hédan from the University of Rennes and his colleagues, published on April 8 in the open access journal PLOS Genetics. The results confirm a tumor suppressor gene known as a risk factor for histiocytic sarcoma – a rare and aggressive blood cancer that affects both dogs and humans – as well as the identification of four new genetic loci associated with the disease.
Researchers sequenced genomics DNA Extracts of blood samples from Bernese Mountain Dogs, Rottweilers, Flat Coated Retrievers and Golden Retrievers, including 172 dogs diagnosed with Histiocytic Sarcoma (HS) and 128 unaffected dogs An associated genome-wide analysis identified five chromosomal regions that cumulatively increased the risk of HS in all three races. Each of these regulatory regions accounted for 5-15% of cases, which may indirectly influence cancer risk.
Dogs carrying five or more of these mutations had a very high risk of developing blood cancer during their lifetime. Extensive analysis including sequences of dogs diagnosed with two other blood cancers revealed that three of the five chromosomal regions associated with HS had multi-cancer effects, increasing the risk of lymphomas, osteosarcomas in Rottweilers and tumors. mast cells in Bernese mountain dogs and retrievers. .
Bernese Mountain Dogs have a high incidence of familial cancers: histiocytic sarcoma (in black), lymphoma (in blue) and mast cell tumor (in green). This breed represents a unique model for disentangling the genetics of the corresponding human cancers, due to strong predispositions to cancer, due to the founding effects and artificial selection applied by humans on canine breeds. Photo taken by Chantal Orellou. Credit: Hédan B et al., 2021, PLOS Genetics
Previous studies have used domestic dogs as a model to study the genetics of rare human cancers, but this is the largest multiracial study of HS to date. The authors hope the findings can help inform our understanding of human HS, a cancer for which there are few diagnostic tools and limited clinical options. For example, several of the variants identified in the present study have already been linked to a predisposition to cancer, immune system function or allergies in humans.
“This study took advantage of the predispositions of the canine breed to decipher the genetic bases of histiocytic sarcoma, a rare human cancer”, conclude the authors. “We have shown that the risk of developing this cancer results from the accumulation of genetic alterations in several chromosomal regions linked to the function of the immune system and to different predispositions to cancers, providing candidate genes relevant for the corresponding human cancers.”
Reference: “Identification of predisposing loci common to hematopoietic cancers in four breeds of dogs” by Hédan B, Cadieu É, Rimbault M, Vaysse A, Dufaure de Citres C, Devauchelle P, et al., April 8, 2021, PLOS Genetics.
DOI: 10.1371 / journal.pgen.1009395
Funding: CA received funding from INCa PLBio (“Rare canine tumors” grant (N ° 2012-103; 2012-2016) and Aviesan (Grant MTS 2012-06) for the work described here. BH received funding from the American Kennel Club Canine Health Funding (grant N 2446). This research is also funded by the ANR (grant ANR-11-INBS-0003). Donors played no role in the design study, data collection and analysis, publication decision or manuscript preparation.
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