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. 2023 Sep 7;13(18):2846.
doi: 10.3390/ani13182846.

Canine Somatic Mutations from Whole-Exome Sequencing of B-Cell Lymphomas in Six Canine Breeds-A Preliminary Study

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Canine Somatic Mutations from Whole-Exome Sequencing of B-Cell Lymphomas in Six Canine Breeds-A Preliminary Study

Sungryong Kim et al. Animals (Basel). .

Abstract

Canine lymphoma (CL) is one of the most common malignant tumors in dogs. The cause of CL remains unclear. Genetic mutations that have been suggested as possible causes of CL are not fully understood. Whole-exome sequencing (WES) is a time- and cost-effective method for detecting genetic variants targeting only the protein-coding regions (exons) that are part of the entire genome region. A total of eight patients with B-cell lymphomas were recruited, and WES analysis was performed on whole blood and lymph node aspirate samples from each patient. A total of 17 somatic variants (GOLIM4, ITM2B, STN1, UNC79, PLEKHG4, BRF1, ENSCAFG00845007156, SEMA6B, DSC1, TNFAIP1, MYLK3, WAPL, ADORA2B, LOXHD1, GP6, AZIN1, and NCSTN) with moderate to high impact were identified by WES analysis. Through a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 17 genes with somatic mutations, a total of 16 pathways were identified. Overall, the somatic mutations identified in this study suggest novel candidate mutations for CL, and further studies are needed to confirm the role of these mutations.

Keywords: B-cell; PARR; canine lymphoma; whole-exome sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Standard bioinformatic analysis pipeline used in this study. The blue boxes show the name of the tools used.
Figure 2
Figure 2
Analysis of somatic tumor variants shows specific highly shared loci. Individual somatic variants shared between at least two subjects were plotted based on the degree of sharing (number of subjects sharing said variant) and the location of each variant on the genome.
Figure 3
Figure 3
Gene-level analysis showing a major PPI network being subjected to somatic mutations: (a) Genes targeted by somatic mutations in multiple subjects were plotted based on the locus of the chromosome and the degree of sharing. (b) Genes targeted by somatic mutations with high or moderate impact in multiple subjects. (c) PPI network of the named genes targeted by shared somatic variants. Nodes with no connections were removed for enhanced visibility, and the built-in hierarchical layout of Cytoscape was used.
Figure 4
Figure 4
Vascular smooth muscle contraction pathway confirmed in the KEGG pathway analysis. The asterisk (*) indicates the genes associated with this pathway.
Figure 5
Figure 5
Calcium signaling pathway confirmed in the KEGG pathway analysis. The asterisk (*) indicates the genes associated with this pathway.
Figure 6
Figure 6
Platelet activation pathway confirmed in the KEGG pathway analysis. The asterisk (*) indicates the genes associated with this pathway.
Figure 7
Figure 7
Stereotypic moderate- to high-impact germline mutations found in lymphoma subjects. The mutation, position, and chromosome based on CanFam3.1 are written within the bar plots with the VEP predicted effect shown as icons. Those with two or more icons have multiple effects assigned.

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