Characterization of an aberrant c-myc gene translocation into the esilon switch region of the IgE-producing rat immunocytoma, IR162

A simple type of reciprocal chromosomal translocation in the LOU rat, IgE-secreting immunocytoma cell line, IR162, involving the cmyc proto-oncogene and the switch region of the epsilon immunoglobulin heavy chain, c-myc/Se, was characterized. This abnormal gene rearrangement in IR162 suggests that the same mechanism responsible for normal Ig gene H-chain class switching to the functional e allele was also probably responsible for the aberrant c-myc gene translocation to the homologous non-functional E allele.

By cloning and sequencing the translocation-associated and the homologous normal c-myc and Se DNAs, the position of the translocational junction in both the c-myc 5'-flanklng region and the repetitive elements of the Se region was identified. The translocational recombination was precise and no Insertion nor N-addition were found at the junctional region, leaving all the c-myc exons, together with their two promoter sites, intact. RNase mapping confirmed that the same promoters were utilized in IR162 and normal LOU rat spleen cells. No point mutation was found in the 5'-flanking region and the 3'-portion of exon 1 of the translocated cmyc gene. However, the putative silencer region was lost with the aberrant translocation. It was also noticed that a strikingly AT-rich DNA sequence, associated with Se region, was juxtaposed to the 5'- flanklng region of the c-myc gene. Therefore, It is tempting to speculate that a change of DNA topology, perhaps either due to the juxtaposition of an AT-rich sequence of the Se region, or to the loss of the putative silencer element, or both, might contribute to c-myc gene deregulation in IR162.