MINIMAL TRUNCATION OF THE C-MYB GENE-PRODUCT IN RAPID-ONSET B-CELL LYMPHOMA

Oncogenic activation of c-myb by insertional mutagenesis has been impl icated in rapid-onset B-cell lymphomas induced by the nonacute avian l eukosis virus EU-8. In these tumors. proviruses are integrated either upstream of the c-myb coding region or within the first intron of c-my b. Tumors with either type of integration contained identical chimeric mRNAs in which the viral 5' splice site was juxtaposed to the 3' spli ce site of c-myb exon 2 and myb exon 1 was eliminated, Both classes of integrations generated truncated Myb proteins that were indistinguish able by Western analysis. In contrast to most other examples of c-myb activation, the truncation consisted of only 20 N-terminal amino acids and did not disrupt either the DNA binding domain near the N terminus or the negative regulatory domain near the C terminus of Myb. The sig nificance of tile 20-amino-acid Myb truncation to tumorigenesis was te sted by infection of chicken embryos with retroviral vectors expressin g different myb gene products, While virus expressing either wild-type c-myb or c-myb mutated at the N-terminal casein kinase II sites was o nly weakly oncogenic at 10 weeks, the minimally truncated myb virus in duced a high incidence of rapid-onset tumors, including B-cell lymphom as, sarcomas, and adenocarcinomas.