Translocation of the myc cellular oncogene to the immunoglobulin heavy chain locus in murine plasmacytomas is an imprecise reciprocal exchange

Abstract

The 15;12 translocations in murine plasmacytomas represent recombination of the myc oncogene with the immunoglobulin CH locus, often within CH switch recombination (SH) regions. Chromosome junctions cloned from four plasmacytomas confirmed that the translocation generates reciprocal CHSH-myc and 5'myc-SH structures. H locus targets included S alpha fused to Smu, Smu fused to S gamma 2b, and a germline S alpha region. The nature of two H locus targets suggests that the target need not be highly active transcriptionally. Switch recombination machinery is implicated in the translocation by the SH targets and by homology of certain c-myc breakpoints with normal switch recombination sites. Fusion regions revealed deletions, extraneous nucleotides, and one duplication. These results prompt a translocation model in which staggered single-stranded breaks on each chromosome are followed by single-strand excision or polymerization prior to ligation to the other chromosome.