Friday , May 14 2021

Genetic mutations add up to a very high risk of blood cancer in three popular dog breeds

Bernese mountain dog

The genomic study identifies cancer-related variants in mountain dogs, Rottweilers and retrievers.

Six genetic variants are added to determine the risk of several blood cancers in dog breeds already available, according to a study by Benoît Hédan at the University of Rennes et al., Published April 8 in the open access journal Genetics PLOS. The results confirm a known tumor suppression gene 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 sites associated with the disease.

The researchers sequenced the genomic DNA were extracted from blood samples from Bernese mountain dogs, Rottweilers, flat-coated retrievers and gold retrievers, including 172 dogs diagnosed with histocytic sarcoma (HS) and 128 untreated dogs. An analysis of relatives across the genome identified five chromosomal regions that cumulatively increased the risk of HS in the three breeds. Each of these regulatory regions accounted for 5-15% of cases, which may indirectly affect cancer risk.

Dogs carrying five or more of these mutations had a very high risk of developing blood cancer during their lifetime. An extensive analysis of sequences from dogs diagnosed with two other blood cancers found that three of the five HS-related chromosomal regions had multiple cancerous effects, increasing the risk of lymphoma, osteosarcomas in Rottweilers and tumors in patients. Bernese mountains. .

Cancer genetics of dogs of the Bernese mountains

Bernese dogs have a high incidence of familial cancers: histiocytic sarcoma (in black), lymphoma (in blue) and mast cells (in green). This breed represents a unique model for revealing the genetics of the respective human cancers, due to the strong predisposition to cancer, due to the founding results and the artificial selection that humans apply to dog breeds. The photo was taken by Chantal Orellou. Credit: Hédan B et al., 2021, PLOS Genetics

Previous studies have used pets as a model to study the genetics of rare cancers in humans, but this is the largest multi-breed HS study to date. The authors hope the results can help update our understanding of human HS, a cancer for which there are few diagnostic tools and limited clinical options. For example, many of the variants identified in the present study have previously been linked to predisposition to cancer, immune system function, or allergies in humans.

“This study exploited the intentions of dog breeds to decipher the genetic basis of histocellular sarcoma, a rare human cancer,” the authors conclude. “We have shown that the risk of developing this cancer results from the accumulation of genetic lesions from different chromosomal regions associated with the functioning of the immune system and from a different predisposition to cancer, providing relevant candidate genes for the respective human cancers.”

Reference: “Identification of common predisposing sites in hematopoietic cancers in four dog breeds” by Hédan B, Cadieu É, Rimbault M, Vaysse A, Dufaure de Citres C, Devauchelle P, et al., April 8, 2021, Genetics PLOS.
DOI: 10.1371 / journal.pgen.1009395

Funding: CA received funding from INCa PLBio (Grant Rare Dogs Grant (Nos. 2012-103, 2012-2016) and Aviesan (Grant MTS 2012-06) for the project described here. American Kennel Club Canine Health Funding (Grant N 2446) This research is also funded by ANR (Grant ANR-11-INBS-0003) The funders had no role in the study design, data collection and analysis decision or in the preparation of the manuscript.

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