MUTATIONS IN THE P53 TUMOR-SUPPRESSOR GENE ARE FREQUENTLY ASSOCIATED WITH BOVINE LEUKEMIA VIRUS-INDUCED LEUKEMOGENESIS IN CATTLE BUT NOT INSHEEP

To investigate the mechanisms of bovine leukemia virus (BLV)-induced l eukemogenesis, we have examined the alterations of the p53 tumor-suppr essor gene in sheep and in cattle. The sequences of the open reading f rames as well as the intron/exon junctions of the ovine and bovine p53 genes were determined. Pathological samples were screened for the pre sence of p53 mutations using a single-strand conformational polymorphi sm assay. Five of ten BLV-induced bovine tumors harbored p53 mutations . In contrast, only one of seven samples corresponding to circulating leukocytes from cattle in persistent lymphocytosis showed an alteratio n of the p53 gene. Surprisingly, no p53 mutation was found among the 1 0 BLV-induced sheep tumors analyzed. Altogether, these data indicate t hat p53 mutations are linked to BLV-induced leukemogenesis in cattle a t the transition to the lymphomic stage. These results also enlighten different molecular mechanisms involved in sheep and in cattle during BLV-induced pathogenesis. (C) 1995 Academic Press, Inc.