A conserved sequence at c-myc oncogene chromosomal translocation breakpoints in plasmacytomas

Many recent studies have shown that chromosomal translocation breakpoints frequently occur near cellular proto-oncogenes (reviewed in ref. 1). In both mouse plasmacytomas and Burkitt lymphomas, the c-myc oncogene becomes joined to an immunoglobulin heavy-chain gene in a head-to-head configuration. Within c-myc, the breaks frequently occur near the first exon-intron boundary, while within the immunoglobulin gene the breaks usually involve sequences directing heavy-chain switching. It has been assumed that the translocations represent abortive immunoglobulin switching events which have activated the c-myc gene for a role in tumour formation. However, sequence analysis of the c-myc gene does not reveal any apparent similarity to the immunoglobulin switch signals. With these results in mind, we have determined the precise breakpoints within c-myc for two plasmacytoma lines in order to search for any common features that may shed some light on the mechanism of chromosomal translocation. We report here that the tetranucleotide sequence GAGG occurs close to the breakpoint in five out of six translocations, and so may be a sequence recognized by either the enzymes that catalyse immunoglobulin heavy-chain switching, or some other DNA-cleaving activity.