Peer-reviewed veterinary case report
DAPK gene hypermethylation predicts worse outcome in dogs
By Sato, M et al.·Published in Veterinary and comparative oncology·2018·Department of Veterinary Internal Medicine, Japan·View original on PubMed →
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Original publication title: Prognostic significance of hypermethylation of death-associated protein kinase (DAPK) gene CpG island in dogs with high-grade B-cell lymphoma.
- Species:
- dog
Plain-English summary
A group of 47 dogs diagnosed with high-grade B-cell lymphoma underwent treatment with a chemotherapy protocol called CHOP, which includes vincristine, cyclophosphamide, doxorubicin, and prednisolone. Researchers found that 21 of these dogs had a specific genetic change (hypermethylation of the DAPK gene) that was linked to a poorer outcome. Dogs with this genetic change had shorter survival times, with a median of about 220 days compared to 301 days for those without it. This suggests that hypermethylation of the DAPK gene can be a sign of a more aggressive form of lymphoma in dogs, indicating a need for closer monitoring and possibly more aggressive treatment.
People also search for: dog lymphoma prognosis · high-grade B-cell lymphoma in dogs · DAPK gene hypermethylation in dogs
Abstract
Death-associated protein kinase (DAPK) is a serine/threonine kinase and a tumour suppressor gene. Diffuse large B-cell lymphomas with inactivated DAPK through hypermethylation of a CpG island is known to result in a biologically aggressive phenotype in humans. This retrospective study was carried out to analyse the prognostic significance of DAPK CpG island hypermethylation in canine lymphoma. We hypothesized that DAPK CpG island hypermethylation can be a negative prognostic indicator in dogs with nodal high-grade B-cell lymphoma. Forty-seven dogs with high-grade B-cell lymphoma, according to the updated Kiel classification, were evaluated after being treated with a CHOP (vincristine, cyclophosphamide, doxorubicin and prednisolone)-based chemotherapy protocol. The methylation status of the DAPK CpG island was examined by methylation-specific PCR. Progression-free survival (PFS) and overall survival (OS) were compared using the Kaplan-Meier analysis and log-rank test. The cox proportional hazard regression model was used to evaluate the effect of multiple variables. Hypermethylation of the DAPK CpG island was detected in 21 of the 47 dogs. The PFS and OS in dogs with the hypermethylation (median: 220 and 266 days, respectively) were significantly shorter than those of dogs without hypermethylation (median: 301 and 412 days, respectively) (PFS, P = .036; OS, P = .007). In the multivariate analysis, hypermethylation of the DAPK CpG island remained an independent prognostic factor in predicting shortened PFS (P = .047) and OS (P = .021) as well as clinical substage b. Overall, hypermethylation of the DAPK CpG island was a negative prognostic factor in canine high-grade B-cell lymphoma.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/29527805/