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.
Katz
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Department of Virology, Weizmann Institute of Science, Rehovot, Israel.
Kahana
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D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D000518:Eflornithine / Q000494:pharmacology; D005784:Gene Amplification; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D005809:Genes, Regulator; D005812:Genes, Switch; D051379:Mice; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000276:immunology
D004247:DNA; D009955:Ornithine Decarboxylase; D000518:Eflornithine