Friday , May 7 2021

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

Bernese Mountain Dog

A genomic study finds cancer-related variants in Bernese Mountain Dogs, Rottweilers and Retrievers.

Six genetic variants are being collected to determine the risk of several blood cancers in predisposed dog breeds, according to a study by Benoit Hedan of the University of Rennes and colleagues, published April 8 in an open access journal. PLOS Genetics. The results confirm the known gene for tumor suppression 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.

The researchers sequenced the genomics DNA taken from blood samples from Bernese Mountain Dogs, Rottweilers, Flat Coated Retrievers and Golden Retrievers, including 172 dogs diagnosed with histiocytic sarcoma (HS) and 128 dogs without disease. Genome-wide analysis of associates identified five chromosomal regions that cumulatively increased the risk of HS in three races. Each of these regulatory regions accounted for 5-15% of cases, which may indirectly affect cancer risk.

Dogs that carried five or more of these mutations had a very high risk of developing blood cancer during their lifetime. An extended analysis involving dog sequences diagnosed with two more blood cancers revealed that three of the five chromosomal regions associated with HS had multicancer effects, increasing the risk of lymphoma, osteosarcoma in Rottweilers, and mast cell tumors in Bernese Mountain Dogs and Retrievers.

Cancer genetics of Bernese Mountain Dogs

Bernese Mountain Dogs have a high incidence of familial cancers: histiocytic sarcoma (black), lymphoma (blue) and mast cell tumor (green). This breed is a unique model for detecting the genetics of relevant human cancers, thanks to its strong predisposition to cancer, due to the effects of the founders and the artificial selection that humans apply to dog breeds. Recorded by Chantal Orellou. Credits: Hedan 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 HS study to date. The authors hope that the results may help to understand human HS, a cancer for which there are few diagnostic tools and limited clinical possibilities. For example, several variants identified in this study have previously been linked to a predisposition to cancer, immune system function, or allergies in humans.

“This study used the predispositions of the dog breed to decipher the genetic basis of histiocytic sarcoma, a rare human cancer,” the authors conclude. “We have shown that the risk of developing this cancer arises from the accumulation of genetic changes from several chromosomal regions associated with immune system function and different predispositions to cancer, providing relevant genes that are candidates for appropriate cancer in humans.”

Reference: “Identification of common predisposing loci of hematopoietic carcinomas in four breeds of dogs”, by Hedan B, Cadieu E, Rimbault M, Vaisse 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 (grant for “dog rare tumors” (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 Financing (grant N 2446) This research is also funded by ANR (grant ANR-11-INBS-0003).

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