Deregulated expression of c-Myc in a translocation-negative plasmacytoma on extrachromosomal elements that carry IgH and myc genes
| Autor: | Theodore I. Kuschak, Sabine Mai, Shinsuke Ohno, Francis Wiener |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Chromosomal translocation
In situ hybridization Biology Translocation Genetic Proto-Oncogene Proteins c-myc Mice Histone H3 Extrachromosomal DNA medicine Animals Humans Gene Chromosome 12 Gene Rearrangement Genetics Mice Inbred BALB C Multidisciplinary Karyotype Biological Sciences medicine.disease Molecular biology Blotting Southern Gene Expression Regulation Plasmacytoma Female Immunoglobulin Heavy Chains |
| Zdroj: | Proceedings of the National Academy of Sciences. 96:13967-13972 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.96.24.13967 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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