Amplification of the translocated c-myc genes in three Burkitt lymphoma cell lines.
Translocations of the coding exons of the human c-myc gene are consistent features of human Burkitt lymphomas (BL). In the BL cell lines CA46, JD40, and ST486, the second and third c-myc exons have been translocated into the immunoglobulin heavy chain locus. In addition to this rearrangement, in all three cell lines, we have found that the translocated c-myc exons show low-level amplification relative to restriction fragments from the germ-line c-myc gene. The patterns of hybridization of an IgM switch region probe suggest that immunoglobulin heavy chain sequences have been co-amplified with the translocated c-myc sequences. Differential sedimentation was used to determine whether the amplified sequences reside in high-molecular-weight chromosomes or low-molecular-weight extrachromosomal DNA. In JD40 and ST486 cells, the amplified c-myc sequences were found on high-molecular-weight chromosomes ST486 cells also contained translocated C-myc sequences in low-molecular-weight, extrachromosomal DNA, as did CA46 cells. These conclusions were corroborated by fluorescence in-situ hybridization (FISH) of HeLa, CA46, ST486 and JD40 metaphase chromosomes. These results suggest that there is ongoing selection for cells containing amplified copies of the expressed c-myc sequences. and that there is continuous generation of extrachromosomal copies of the translocated c-myc sequences in ST486 and CA46 cells.
Khaira
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P
Department of Biochemistry and Molecular Biology, Wright State University, Dayton, OH 45435, USA.
James
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CD
Leffak
M
M
D002051:Burkitt Lymphoma / Q000235:genetics*; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D005091:Exons / Q000235:genetics; D005784:Gene Amplification / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008970:Molecular Weight; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D007143:Immunoglobulin Heavy Chains