The tree that hides the forest: identification of common predisposing loci in several hematopoietic cancers and several dog breeds

摘要: Histiocytic sarcoma (HS) is a rare but aggressive cancer in humans and dogs. The spontaneous canine model, with the clinical, epidemiological histological similarities human HS specific breed predispositions, unique model/opportunity to unravel genetic bases of this cancer. In study, we aimed identify germline risk factors associated development predisposed breeds. We used methodology that combined several genome-wide association studies multi-breed multi-cancer approach, as well targeted next generation sequencing, imputation combining breeds (Bernese mountain dog, Rottweiler, flat coated retriever golden retriever) three haematopoietic cancers (HS, lymphoma mast cell tumor). Results showed not only refined previously identified CDKN2A locus new loci on chromosomes 2, 5, 12, 14, 20, 26 X. Capture sequencing pointed towards existence regulatory variants non coding regions and/or methylation mechanisms linked haplotypes, leading strong predispositions dog Our results these predisposing appear be due additive effect haplotype involved also other such or tumor, illustrating pleiotropic nature observed oncology, thus reinforcing interest study initiation progression.