Rearrangement between ornithine decarboxylase and the switch region of the gamma 1 immunoglobulin gene in alpha-difluoromethylornithine resistant mouse myeloma cells.

We demonstrate here that the functional ornithine decarboxylase (ODC) gene of alpha-difluoromethylornithine (alpha-DFMO, a suicide inhibitor of ODC) resistant mouse myeloma 653-1 cells has been rearranged with the immunoglobulin heavy chain locus in a c-myc like manner. Structural analysis of a molecular clone representing this gene revealed that it is joined in a head to head configuration to the switch region of the gamma 1 immunoglobulin gene. Comparison of this rearranged ODC gene to a germline ODC gene isolated from mouse liver DNA revealed identity in the region downstream to the breakpoint which was mapped to position -1371 +/- 1 relative to the transcription initiation site (position +1). In the switch region of the gamma 1 immunoglobulin gene the breakpoint falls within a 49 bp repeat, in a sequence frequently involved in class switching. This finding further supports the notion that in B cells the immunoglobulin gene clusters are prone to random rearrangements which under selection for a tumorigenic phenotype involve oncogenes. However, as demonstrated here, employment of specific pharmacological selection can reveal rearrangements with non-oncogenic genes.