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



Bernese Mountain Dog

Genomic studies have found cancer-related mutations in Bernese Mountain Dogs, Rottweilers and Hunting Dogs.

A study published by Benoît Hédan and colleagues at the University of Rennes in an open access journal on April 8 showed that the combination of six gene variants can determine the risk of several blood cancers in predisposed dog breeds. PLOS genetics. The results confirmed that the known tumor suppressor gene is a risk factor for histocytic sarcoma (a rare aggressive blood cancer that affects both dogs and humans), and identified four new gene loci related to the disease.

Researchers sequenced the genome DNA Blood samples taken from Bernese Mountain Dogs, Rottweilers, Flat Coated Retrievers and Golden Retrievers, including 1

72 dogs diagnosed with histocytosarcoma (HS) and 128 unaffected dogs. Genome-wide association analysis identified five chromosomal regions, which cumulatively increased the risk of HS in three varieties. Each of these regulatory areas accounts for 5-15% of cases, which may indirectly affect cancer risk.

Dogs with five or more of these mutations are very likely to develop blood cancer in their lifetime. The extended analysis included the sequences of dogs diagnosed with two other blood cancers, and found that three of the five chromosomal regions associated with HS have a polycancerous effect, increasing the lymphoma, osteosarcoma, and osteosarcoma of the Bernese Mountain Dog and Hunting Dog The risk of mast cell tumor.

Bernese Mountain Dog Cancer Genetics

Bernese Mountain Dogs present a high incidence of familial cancers: histocytosarcoma (black), lymphoma (blue) and mast cell tumor (green). Due to the strong cancer susceptibility (due to the founder’s influence on humans and the artificial selection of dog breeds), this breed represents a unique model that can reveal the genetics of corresponding human cancers. Photo taken by Chantal Orellou. Image source: 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 HS multi-breed study conducted to date. The authors hope that these results will help us understand human HS, a cancer with few diagnostic tools and limited clinical options. For example, several variants identified in this study have previously been associated with human cancer susceptibility, immune system function or allergies.

The authors concluded: “This study uses the susceptibility of dog breeds to decipher the genetic basis of a rare human cancer histocytosarcoma.” “We show that the risk of this cancer is due to immune system function. The accumulation of genetic changes in multiple chromosomal regions related to the susceptibility of different cancers provides relevant candidate genes for corresponding human cancers.”

References: Hédan B, CadieuÉ, Rimbault M, Vaysse A, Dufaure de Citres C, Devauchelle P, etc., “The identification of common susceptibility gene loci in four dog breeds and hematopoietic cancers”, April 8, 2021 , PLOS genetics.
DOI: 10.1371/journal.pgen.1009395

Funding: CA received funding from INCa PLBio (granted “Canine Rare Oncology” funding (2012-103; 2012-2016) and Aviesan (granted MTS 2012-06)), and BH received funding from American Kennel Club Canine. Health Grant (Grant N 2446). The research is also funded by ANR (Grant ANR-11-INBS-0003). The funder has no role in research design, data collection and analysis, and decision to publish or write the manuscript.




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