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DNA methylation markers linked to longer survival in dogs

By Teoh, Yong Bin et al.·Published in Journal of veterinary internal medicine·2024·Veterinary Teaching Hospital, Japan·View original on PubMed

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Original publication title: Use of genome-wide DNA methylation analysis to identify prognostic CpG site markers associated with longer survival time in dogs with multicentric high-grade B-cell lymphoma.

Species:
dog

Plain-English summary

A group of dogs diagnosed with multicentric high-grade B-cell lymphoma (MHGL) underwent chemotherapy and were studied to find markers that could predict how long they might survive. Researchers discovered that certain changes in DNA methylation (a chemical modification of DNA) could indicate better or worse outcomes. Specifically, dogs with lower levels of methylation at two key sites had significantly longer survival times. This information can help pet owners understand their dog's prognosis and treatment options better.

People also search for: dog lymphoma prognosis · chemotherapy for dog cancer · dog survival rates lymphoma

Abstract

BACKGROUND: DNA methylation analysis might identify prognostic CpG sites in CHOP-treated dogs with multicentric high-grade B-cell lymphoma (MHGL) with heterogenous prognosis. OBJECTIVE: To identify prognostic CpG sites of MHGL through genome-wide DNA methylation analysis with pyrosequencing validation. ANIMALS: Test group: 24 dogs. Validation group: 100 dogs. All client-owned dogs were diagnosed with MHGL and treated with CHOP chemotherapy. METHODS: Cohort study. DNA was extracted from lymph node samples obtained via FNA. Genome-wide DNA methylation analysis using Digital Restriction Enzyme Analysis of Methylation (DREAM) was performed on the test group to identify differentially methylated CpG sites (DMCs). Bisulfite pyrosequencing was used to measure methylation status of candidate DMCs in the validation group. Median survival times (MST) were analyzed using Kaplan-Meier (log-rank) product limit method. RESULTS: DREAM analyzed 101&#x2009;576 CpG sites. Hierarchical clustering of 16&#x2009;262 CpG sites in test group identified group with better prognosis (MST&#x2009;=&#x2009;55-477&#x2009;days vs 10-301&#x2009;days, P&#x2009;=&#x2009;.007). Volcano plot identified 1371 differentially methylated CpG sites (DMCs). DMC near the genes of FAM213A (DMC-F) and PHLPP1 (DMC-P) were selected as candidates. Bisulfite-pyrosequencing performed on validation group showed group with methylation level of DMC-F&#x2009;<&#x2009;40% had favorable prognosis (MST&#x2009;=&#x2009;11-1072&#x2009;days vs 8-1792&#x2009;days, P&#x2009;=&#x2009;.01), whereas group with the methylation level combination of DMC-F&#x2009;<&#x2009;40% plus DMC-P&#x2009;<&#x2009;10% had excellent prognosis (MST&#x2009;=&#x2009;18-1072&#x2009;days vs 8-1792&#x2009;days, P&#x2009;=&#x2009;.009). CONCLUSION AND CLINICAL IMPORTANCE: Methylation status of prognostic CpG sites delineate canine MGHL cases with longer MST, providing owners with information on expectations of potential improved treatment outcomes.

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Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/38115210/