A der(8)t(8;11) chromosome in the Karpas-620 myeloma cell line expresses only cyclin D1: yet both cyclin D1 and MYC are repositioned in close proximity to the 3'IGH enhancer.
The Karpas-620 human myeloma cell line (HMCL) expresses high levels of Cyclin D1 (CCND1), but has a der(8)t(8;11) and a der(14)t(8;14), and not a conventional t(11;14). Fluorescent in situ hybridization (FISH) and array comparative genomic hybridization (aCGH) studies suggest that der(14)t(11;14) from a primary translocation underwent a secondary translocation with chromosome 8 to generate der(8)t(8;[14];11) and der(14)t(8;[11];14). Both secondary derivatives share extensive identical sequences from chromosomes 8, 11, and 14, including MYC and the 3' IgH enhancers. Der(14), with MYC located approximately 700 kb telomeric to the 3'IGH enhancer, expresses MYC. By contrast, der(8), with both CCND1 and MYC repositioned near a 3'IGH enhancer, expresses CCND1, which is telomeric of the enhancer, but not MYC, which is centromeric to the enhancer. The secondary translocation that dysregulated MYC resulted in extensive regions from both donor chromosomes being transmitted to both derivative chromosomes, suggesting a defect in DNA recombination or repair in the myeloma tumor cell.
Dib
Amel
A
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20889-5101, USA.
Glebov
Oleg K
OK
Shou
Yaping
Y
Singer
Robert H
RH
Kuehl
W Michael
WM
D000818:Animals; D045744:Cell Line, Tumor; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D014178:Translocation, Genetic
C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1; D012313:RNA