LACK OF MUTATION IN THE WAF1 CIP1 GENE DURING BOVINE LEUKEMIA VIRUS-INDUCED LEUKEMOGENESIS/

As a cyclin-dependent kinases (Cdks) inhibitor (CDI), the protein p21( WAF1/CIP1) is able to interfere with cell cycle progression. Its expre ssion is upregulated by wild-type p53, and the p21(WAF1/CIP1) protein appears to be a potent effector of the p53-dependent cell cycle regula tory pathway. We have previously reported that p53 mutations frequentl y occur during bovine leukemia virus (BLV)-induced leukemogenesis in c attle but not in sheep. Therefore, we have investigated the involvemen t of p21(WAF1/CIP1) mutations in the tumorigenic process associated wi th BLV. We first cloned the bovine and ovine WAF1 genes and determined the complete nucleotide sequences of their second coding exons. These sequences share respectively 79% and 80% homology with those of the h uman counterpart exon. In order to screen for mutations that could be associated with BLV-induced pathogenicity, we performed single strand conformation polymorphism (SSCP) assays on the WAF1 genes from BLV-ind uced tumors. No WAF1 mutations were detected in any of the ten BLV-ind uced bovine tumor samples. Among eleven sheep tumors and three ovine c ell lines, only one sample revealed a single mutation in the WAF1 codi ng sequence, but this mutation was silent at the translational level. We concluded that mutations of the WAF1 gene are not involved in the d evelopment of the tumors during BLV-induced leukemogenesis. (C) 1997 E lsevier Science B.V.