Mutations in the tumor suppressor gene p53 in cattle are associated with enzootic bovine leukosis

Abstract

Enzootic bovine leukosis (EBL) is a B-cell lymphoma caused by the bovine leukemia virus (BLV). Although an association between EBL and mutations in the bovine tumor suppressor gene TP53 (bTP53) has been suggested, the substantive incidence rate of bTP53 mutations in EBL cattle is still unclear. In this study, we investigated the complete sequence (exons 2–11) of bTP53 in tissue and peripheral blood leukocyte (PBL) samples obtained from 154 EBL cattle and 117 cattle without EBL (non-EBL cattle) to elucidate the correlation between bTP53 mutations and EBL. The detection frequencies of non-synonymous (NS) and deletion mutations in bTP53 in EBL cattle were significantly higher than those in non-EBL cattle in both tissue and PBL samples (p < 0.05). Among these mutations in EBL cattle, 73.7 % (42/54) were homologous to those of human TP53 (hTP53), which were previously detected in various tumors. It has been reported that 95.2 % (40/42) of these hTP53 mutations induced complete or partial loss of the transactivating function of its encoding protein, P53. Moreover, the BLV proviral load in tissue samples was significantly higher in cattle harboring bTP53 NS and deletion mutations than in cattle without these mutations in both EBL and BLV-infected non-EBL cattle (p < 0.05). Although the activity of the mutant variants of bP53 must be further investigated, our findings revealed that bTP53 mutations are involved in tumorigenesis in BLV-infected cells and EBL-associated carcinogenesis.