Genetic mutations increase the risk of very high blood cancer in three popular dog breeds

Barnes Mountain Dog

Genomic studies can detect cancer-linked variants in Bernice mountain dogs, Rottweilers and retrievers.

Six genetic variants will be added to pre-disposed dog breeds to determine the risk of multiple blood cancers, according to a study by Benoit Hayden and colleagues at the University of Rennes, published in the April Open Access Access Journal. PLOS Heredity. The results confirm a tumor-suppressing gene known as a risk factor for histiocytic sarcoma – a rare and invasive blood cancer that affects both dogs and humans – as well as identifying four new genetic loci associated with the disease.

The researchers sequenced the genomics DNA Blood samples were taken from Bernice Mountain Dogs, Rottweilers, Flat-Coated Retrievers, and Golden Retrievers, including 172 dogs diagnosed with Histocytic Sarcoma (HS), and 128 affected dogs. Genome-wide collaborative analysis identified five chromosomal regions that increased the risk of HS in three species. Each of these regulatory areas accounts for 5-15% of cases, which can indirectly affect the risk of cancer.

Five or more of these mutated dogs had a much higher risk of developing blood cancer during their lifetime. Detailed analysis of the other two blood cancer diagnoses, including dog sequences, found that three of the five chromosomal fields associated with HS had a multi-cancer effect, including lymphomas, te stioscomas in Rottweilers, and Bernis mountain dogs in retrieval and resuscitation. .

Bernice Mountain Dogs Cancer Genetics

Bernice mountain dogs represent the highest incidences of familial cancer: histiocytic sarcoma (black), lymphoma (blue), and mast cell tumors (green). Due to the founding effects and artificial selection by the dog breed men, due to the effective cancer predisposition, this breed presents a unique model for dissociating the genetics of the respective human cancers. Picture taken by Chantelle Orello. Credit: Hayden B. et al., 2021, plus heredity

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

“This study took advantage of dog breed hypotheses to explain the genetic basis of histiocytic sarcoma, a rare human cancer,” the authors conclude. “We have shown that the risk of developing this cancer results from the accumulation of genetic changes from many chromosomal regions associated with the function of the immune system and to various cancer conditions, providing relevant candidate genes for related human cancers.”

References: “Identification of a common predisposition to hematopoietic cancer in four dog breeds” Hayden B, Kedia É É, Rimbult M, Vaise A, Dufurer de Citrus C, Devouchel P, et al. PLOS Heredity.
DOI: 10.1371 / journal.pgen.009395

Funding: CA received funding from INCA PLBO (Grant “Canine Rare Tumor” Funding (N ° 2012-103; 2012-2016)) and Avison (Grant MTS 2012-06) for the work described here. BH received funding from the American Kennel Club Canine Health Fund (Grant N2446). This research is also funded by ANR (Grant ANR-11-INBS-0003). Funding had no role in study design, data collection and analysis, decision to publish, or manuscript preparation.