Deregulated expression of c-Myc in a translocation-negative plasmacytoma on extrachromosomal elements that carry IgH and myc genes.
The induced expression of c-Myc in plasmacytomas in BALB/c mice is regularly associated with nonrandom chromosomal translocations that juxtapose the c-myc gene to one of the Ig loci on chromosome 12 (IgH), 6 (IgK), or 16 (IgL). The DCPC21 plasmacytoma belongs to a small group of plasmacytomas that are unusual in that they appear to be translocation-negative. In this paper, we show the absence of any c-myc-activating chromosomal translocation for the DCPC21 by using fluorescent in situ hybridization, chromosome painting, and spectral karyotyping. We find that DCPC21 harbors c-myc and IgH genes on extrachromosomal elements (EEs) from which c-myc is transcribed, as shown by c-myc mRNA tracks and extrachromosomal gene transfer experiments. The transcriptional activity of these EEs is supported further by the presence of the transcription-associated phosphorylation of histone H3 (H3P) on the EEs. Thus, our data suggest that in this plasmacytoma, c-Myc expression is achieved by an alternative mechanism. The expression of the c-Myc oncoprotein is initiated outside the chromosomal locations of the c-myc gene, i.e., from EEs, which can be considered functional genetic units. Our data also imply that other "translocation-negative" experimental and human tumors with fusion transcripts or oncogenic activation may indeed carry translocation(s), however, in an extrachromosomal form.
Wiener
F
F
Microbiology and Tumorbiology Center, Karolinska Institute, S-171 77 Stockholm, Sweden.
Kuschak
T I
TI
Ohno
S
S
Mai
S
S
D000818:Animals; D015139:Blotting, Southern; D005260:Female; D005786:Gene Expression Regulation; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D010954:Plasmacytoma / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D016271:Proto-Oncogene Proteins c-myc