Activation of a translocated c-myc gene: role of structural alterations in the upstream region.

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Abstract
The translocated c-myc gene in AW-Ramos, a [murine] Burkitt lymphoma cell line carrying the 8;14 translocation, is expressed at 2- to 5-fold higher levels than C-myc in lymphoblastoid cell lines. The translocation event has joined c-myc to the IgM switch region. As a consequence, a recently identified Ig transcriptional enhancer element is not linked to the translocated c-myc gene. Chromosomal recombination occurs .simeq. 340 nucleotides upstream of the C-myc 5'' cap site, leaving all 3 c-myc exons intact. The nucleotide sequences of the 2 coding exons in the translocated c-myc gene are identical to those of the normal c-myc gene. Nucleotide sequence analyses of the 1st, noncoding c-myc exon and of the region between this exon and the chromosomal recombination point reveal 2 single-base differences from normal c-myc. Altered expression rather than an altered gene product is responsible for c-myc activation in AW-Ramos cells and that this is a result of either loss of regulatory sequences located > 340 nucleotides upstream of c-myc or dispruption of normal c-myc regulation by 1 or both base substitutions is indicated. Alternatively, unidentified enhancer-like sequences in the Ig locus may alter the expression of c-myc.