Peer-reviewed veterinary case report
Genetic mutations linked to survival in dog lymphoma tumors
By van der Heiden, Anna Darlene et al.·Published in Scientific reports·2025·Department of Medical Biochemistry and Microbiology·View original on PubMed →
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Original publication title: Characterization of the genomic landscape of canine diffuse large B-cell lymphoma reveals recurrent H3K27M mutations linked to progression-free survival.
- Species:
- dog
Plain-English summary
A study looked at dogs with diffuse large B-cell lymphoma (DLBCL), an aggressive type of cancer. Researchers found specific genetic mutations, particularly in a gene called H3K27M, that were linked to how long dogs lived without their cancer worsening. They discovered that these mutations could affect how genes are expressed, which might help explain the cancer's progression. This research highlights the importance of understanding genetic changes in canine DLBCL and suggests that targeting these mutations could lead to new treatment options for affected dogs.
People also search for: dog lymphoma treatment · canine DLBCL symptoms · H3K27M mutation in dogs
Abstract
Diffuse large B-cell lymphoma (DLBCL) is an aggressive hematopoietic neoplasm that affects humans as well as dogs. While previous studies on canine DLBCL (cDLBCL) have significantly advanced our understanding of the disease, the majority of this research has relied on whole-exome sequencing, which is limited in its ability to detect copy number aberrations and other genomic changes beyond coding regions. Furthermore, many of these studies lack sufficient clinical follow-up data, making it difficult to draw meaningful associations between genetic variants and patient outcomes. Our study aimed to characterize the mutational landscape of cDLBCL using whole-genome sequencing of matched tumor-normal samples obtained from a cohort of 43 dogs previously enrolled in a clinical trial for which longitudinal follow-up was available. We focused on identifying genes that were significantly or recurrently mutated with coding point mutations, copy number aberrations, and their associations with patient outcomes. We identified 26 recurrently mutated genes, 18 copy number gains, and 8 copy number losses. Consistent with prior studies, the most commonly mutated genes included TRAF3, FBXW7, POT1, TP53, SETD2, DDX3X and TBL1XR1. The most prominent copy number gain occurred on chromosome 13, overlapping key oncogenes such as MYC and KIT, while the most frequent deletion was a focal loss on chromosome 26, encompassing IGL, PRAME, GNAZ, RAB36, RSPH14, and ZNF280B. Notably, our set of recurrently mutated genes was significantly enriched with genes involved in epigenetic regulation. In particular, we identified hotspot mutations in two histone genes, H3C8, and LOC119877878, resulting in H3K27M alterations predicted to dysregulate gene expression. Finally, a survival analysis revealed that H3K27M mutations in H3C8 were associated with increased hazard ratios for progression-free survival. No copy number aberrations were associated with survival. These findings underscore the critical role of epigenetic dysregulation in cDLBCL and affirm the dog as a relevant large animal model for interrogating the biological activity of novel histone-modifying treatment strategies.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/39922874/