Activation of a translocated c-myc gene: role of structural alterations in the upstream region.
The translocated c-myc gene in AW-Ramos, a 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 immunoglobulin transcriptional enhancer element is not linked to the translocated c-myc gene. Chromosomal recombination occurs approximately equal to 340 nucleotides upstream of the c-myc 5' cap site, leaving all three c-myc exons intact. The nucleotide sequences of the two coding exons in the translocated c-myc gene are identical to those of the normal c-myc gene. Nucleotide sequence analyses of the first, noncoding c-myc exon and of the region between this exon and the chromosomal recombination point reveal two single-base differences from normal c-myc. Our data indicate that 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 greater than 340 nucleotides upstream of c-myc or disruption of normal c-myc regulation by one or both base substitutions. Alternatively, unidentified enhancer-like sequences in the Ig locus may alter the expression of c-myc.
D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D002460:Cell Line; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics; D008223:Lymphoma / Q000235:genetics*; D009154:Mutation; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D012333:RNA, Messenger / Q000378:metabolism; D011995:Recombination, Genetic; D014178:Translocation, Genetic
D007075:Immunoglobulin M; D012333:RNA, Messenger