Aberrant splicing events that are induced by proviral integration: implications for myb oncogene activation.

Activation of the mouse c-myb oncogene in Abelson virus-induced plasmacytoid lymphosarcomas was studied using cDNA cloning and nucleotide sequence analysis. The results presented here show that viral integration in the myb locus generates splicing errors at the 5' and 3' regions. Viral integration results in transcriptional initiation within the viral long terminal repeat and generation of a chimeric mRNA that lacks the first three coding exons. The alterations at the 3' end are caused by an aberrant splicing event in which additional splice-donor and -acceptor sequences within intronic sequences are used to splice an additional 363 nucleotides into the myb transcripts. The resulting insertion of 121 amino acids is in a region of the protein where other activated forms of the myb gene product have deletions. These results suggest that alterations in the 3' end of the myb gene play a crucial role in the activation of this gene.