Mutation of p53 Gene and Its Correlation with the Clinical Outcome in Dogs with Lymphoma

Abstract Background p53 plays a key role in the apoptotic event induced by chemotherapeutic agents. Mutation of p53 gene has been observed in various spontaneous tumors in humans and is associated with a poor prognosis. p53 abnormalities have been evaluated in several tumors in dogs; however, the association of p53 gene mutation with clinical outcome in dogs with lymphoma has not been documented. Hypothesis/Objectives The aim of this study was to examine p53 mutation in canine lymphoma cells and its association with the clinical outcome. Animals Forty-three dogs with previously untreated high-grade lymphoma referred to the University of Tokyo were included in this study. Methods Prospective cohort study. We examined p53 gene (exon 4–8) mutation in the tumor tissues from 43 dogs with lymphoma using PCR-SSCP (polymerase chain reaction – single-strand conformational polymorphism) analysis, followed by nucleotide sequencing of the abnormal bands. Results Of the 43 dogs, 7 dogs (16%) had p53 mutation, whereas 36 dogs (84%) were devoid of p53 mutation. Overall response rate after remission induction was significantly lower (33% versus 88%, P = .002) in dogs with lymphomas having p53 mutation than those with lymphomas devoid of p53 mutation. Overall survival time was significantly shorter (67 days versus 264 days, P = .004) in dogs with lymphoma with p53 mutation than those with lymphoma retaining wild-type p53. Conclusion and Clinical Importance Mutations of p53 gene were detected in a proportion of canine lymphoma cells from untreated dogs and can be associated with a poor prognosis.