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

2020 ◽  
Author(s):  
Benoit Hédan ◽  
Edouard Cadieu ◽  
Maud Rimbault ◽  
Amaury Vaysse ◽  
Patrick Devauchelle ◽  
...  
Keyword(s):  
Mast Cell ◽  
Association Studies ◽  
Canine Model ◽  
Cell Tumor ◽  
Risk Haplotype ◽  
Genome Wide Association Studies ◽  
Targeted Next Generation Sequencing ◽  
Regulatory Variants ◽  
Mast Cell Tumor ◽  
Canine Cancer

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

scholarly journals Identification of common predisposing loci to hematopoietic cancers in four dog breeds

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009395 ◽  
Author(s):  
Benoît Hédan ◽  
Édouard Cadieu ◽  
Maud Rimbault ◽  
Amaury Vaysse ◽  
Caroline Dufaure de Citres ◽  
...  
Keyword(s):  
Mast Cell ◽  
Association Studies ◽  
Canine Model ◽  
Genome Wide Association Studies ◽  
Targeted Next Generation Sequencing ◽  
Mast Cell Tumors ◽  
Regulatory Variants ◽  
Mast Cell Tumor ◽  
Canine Cancer ◽  
Hematopoietic Cancers

Histiocytic sarcoma (HS) is a rare but aggressive cancer in both humans and dogs. The spontaneous canine model, which has clinical, epidemiological, and histological similarities with human HS and specific breed predispositions, provides a unique opportunity to unravel the genetic basis of this cancer. In this study, we aimed to identify germline risk factors associated with the development of HS in canine-predisposed breeds. We used a methodology that combined several genome-wide association studies in a multi-breed and multi-cancer approach as well as targeted next-generation sequencing, and imputation We combined several dog breeds (Bernese mountain dogs, Rottweilers, flat-coated retrievers, and golden retrievers), and three hematopoietic cancers (HS, lymphoma, and mast cell tumor). Results showed that we not only refined the previously identified HS risk CDKN2A locus, but also identified new loci on canine chromosomes 2, 5, 14, and 20. Capture and targeted sequencing of specific loci suggested the existence of regulatory variants in non-coding regions and methylation mechanisms linked to risk haplotypes, which lead to strong cancer predisposition in specific dog breeds. We also showed that these canine cancer predisposing loci appeared to be due to the additive effect of several risk haplotypes involved in other hematopoietic cancers such as lymphoma or mast cell tumors as well. This illustrates the pleiotropic nature of these canine cancer loci as observed in human oncology, thereby reinforcing the interest of predisposed dog breeds to study cancer initiation and progression.

Evaluation of ponatinib in vitro effect in three canine mast cell tumor cell lines expressing FGFR-1, PDGFR-α, and VEGFR-2

2021 ◽  
Vol 269 ◽  
pp. 105621
Author(s):  
C.J. Fisher ◽  
A.T. Lejeune ◽  
M.J. Dark ◽  
O.M. Hernandez ◽  
K. Shiomitsu
Keyword(s):  
Mast Cell ◽  
Tumor Cell ◽  
Cell Lines ◽  
Cell Tumor ◽  
Tumor Cell Lines ◽  
Mast Cell Tumor ◽  
Canine Mast Cell Tumor ◽  
Vitro Effect

scholarly journals RETRACTED ARTICLE: Cutaneous mast cell tumor (Mastocytoma): Cyto- histopathological and haematological investigations

2014 ◽  
Vol 9 (1) ◽  
Author(s):  
Ehsan Hosseini ◽  
Behnam Pedram ◽  
Ali Mohammad Bahrami ◽  
Mohammad Hossein Jaberi Moghaddam ◽  
Javad Javanbakht ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Tumor ◽  
Mast Cell Tumor ◽  
Retracted Article ◽  
Cutaneous Mast Cell

Histologic Grading of Canine Mast Cell Tumor

2014 ◽  
Vol 52 (1) ◽  
pp. 70-73 ◽  
Author(s):  
S. Sabattini ◽  
F. Scarpa ◽  
D. Berlato ◽  
G. Bettini
Keyword(s):  
Mast Cell ◽  
Cell Tumor ◽  
Histologic Grading ◽  
Mast Cell Tumor ◽  
Canine Mast Cell Tumor

Mast cell tumor histamine release following morphine exposure both in vitro and in vivo

2018 ◽  
Vol 45 (6) ◽  
pp. 885.e4
Author(s):  
Taylor Curley ◽  
Pedro Boscan ◽  
Douglas Thamm ◽  
Sam Johnson
Keyword(s):  
Mast Cell ◽  
Histamine Release ◽  
Cell Tumor ◽  
Mast Cell Tumor

scholarly journals A comprehensive integrated post-GWAS analysis of Type 1 diabetes reveals enhancer-based immune dysregulation

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257265
Author(s):  
Seung-Soo Kim ◽  
Adam D. Hudgins ◽  
Jiping Yang ◽  
Yizhou Zhu ◽  
Zhidong Tu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Target Genes ◽  
Association Studies ◽  
Regulatory Elements ◽  
Immune Dysregulation ◽  
Specific Gene ◽  
Genome Wide Association Studies ◽  
Gwas Analysis ◽  
Regulatory Variants

Type 1 diabetes (T1D) is an organ-specific autoimmune disease, whereby immune cell-mediated killing leads to loss of the insulin-producing β cells in the pancreas. Genome-wide association studies (GWAS) have identified over 200 genetic variants associated with risk for T1D. The majority of the GWAS risk variants reside in the non-coding regions of the genome, suggesting that gene regulatory changes substantially contribute to T1D. However, identification of causal regulatory variants associated with T1D risk and their affected genes is challenging due to incomplete knowledge of non-coding regulatory elements and the cellular states and processes in which they function. Here, we performed a comprehensive integrated post-GWAS analysis of T1D to identify functional regulatory variants in enhancers and their cognate target genes. Starting with 1,817 candidate T1D SNPs defined from the GWAS catalog and LDlink databases, we conducted functional annotation analysis using genomic data from various public databases. These include 1) Roadmap Epigenomics, ENCODE, and RegulomeDB for epigenome data; 2) GTEx for tissue-specific gene expression and expression quantitative trait loci data; and 3) lncRNASNP2 for long non-coding RNA data. Our results indicated a prevalent enhancer-based immune dysregulation in T1D pathogenesis. We identified 26 high-probability causal enhancer SNPs associated with T1D, and 64 predicted target genes. The majority of the target genes play major roles in antigen presentation and immune response and are regulated through complex transcriptional regulatory circuits, including those in HLA (6p21) and non-HLA (16p11.2) loci. These candidate causal enhancer SNPs are supported by strong evidence and warrant functional follow-up studies.

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