# Identification of novel genetic mutations for the treatment prognostication of canine lymphoma

**Authors:** Josephine Tsang, Qi Jing Yap, Sheena Kapoor, Jerry Cromarty, Sushmita Sen, Minji Kim, George Courcoubetis, Suhyeon Cho, Deanna Swartzfager, Stanley Park, Sungwon Lim, Ilona Holcomb, Jamin Koo

PMC · DOI: 10.1038/s41698-025-00988-5 · NPJ Precision Oncology · 2025-06-12

## TL;DR

This study identifies genetic mutations in canine lymphoma that are linked to treatment outcomes, offering potential for personalized treatment strategies.

## Contribution

The study reveals novel associations between specific genetic mutations and clinical outcomes in canine lymphoma subtypes.

## Key findings

- TRAF3 mutations are associated with prolonged survival in B-cell lymphomas.
- PIK3CD and CREBBP mutations correlate with poor outcomes in T-cell lymphomas.
- Genomic profiling can improve treatment planning for canine lymphoma.

## Abstract

Canine lymphoma, a phenotypically and genetically heterogeneous disease, represents a significant proportion of canine cancers. We present a large-scale study of 238 dogs with lymphoma to better understand the genetic landscape of canine lymphoma, as well as the relationship to clinical outcomes. Using a targeted next-generation sequencing panel comprising 308 genes, we screened somatic and germline mutations in matched tumor and normal samples. Our findings revealed key associations between genetic alterations and lymphoma subtypes, with certain somatic variants linked to significant differences in response to common chemotherapy regimens. Recurrent mutations in genes such as KMT2C, KMT2D, NOTCH2, TRAF3, CCND1, ARID1A, CREBBP, and TP53 were observed, with TRAF3 mutations standing out for their significant association with prolonged progression-free survival and overall survival in B-cell lymphomas. In contrast, mutations in PIK3CD and CREBBP were associated with inferior outcomes in T-cell lymphomas, highlighting the immunophenotype-specific impact of genetic alterations on treatment responses. These findings support the integration of comprehensive genomic profiling in planning treatment strategies and optimizing clinical outcomes in canine lymphomas.

## Linked entities

- **Genes:** KMT2C (lysine methyltransferase 2C) [NCBI Gene 58508], KMT2D (lysine methyltransferase 2D) [NCBI Gene 8085], NOTCH2 (notch receptor 2) [NCBI Gene 4853], TRAF3 (TNF receptor associated factor 3) [NCBI Gene 7187], CCND1 (cyclin D1) [NCBI Gene 595], ARID1A (AT-rich interaction domain 1A) [NCBI Gene 8289], CREBBP (CREB binding lysine acetyltransferase) [NCBI Gene 1387], TP53 (tumor protein p53) [NCBI Gene 7157], PIK3CD (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) [NCBI Gene 5293]
- **Diseases:** lymphoma (MONDO:0003659)

## Full-text entities

- **Genes:** PIK3CD (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) [NCBI Gene 489644], ARID1A (AT-rich interaction domain 1A) [NCBI Gene 487352], KMT2D (lysine methyltransferase 2D) [NCBI Gene 486558] {aka MLL2}, TP53 (tumor protein p53) [NCBI Gene 403869] {aka P53}, KMT2C (lysine methyltransferase 2C) [NCBI Gene 611094] {aka MLL3}, TRAF3 (TNF receptor associated factor 3) [NCBI Gene 490867], CREBBP (CREB binding protein) [NCBI Gene 479866], NOTCH2 (notch receptor 2) [NCBI Gene 483148], CCND1 (cyclin D1) [NCBI Gene 449028]
- **Diseases:** Canine lymphoma (MESH:D008223), B-cell lymphomas (MESH:D016393), cancers (MESH:D009369), T-cell lymphomas (MESH:D016399)
- **Species:** Canis lupus familiaris (dog, subspecies) [taxon 9615]

## Full text

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## Figures

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## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12162864/full.md

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Source: https://tomesphere.com/paper/PMC12162864