TY - JOUR
T1 - A der(8)t(8;11) chromosome in the Karpas-620 myeloma cell line expresses only Cyclin D1
T2 - Yet both Cyclin D1 and MYC are repositioned in close proximity to the 3′ IGH enhancer
AU - Dib, Amel
AU - Glebov, Oleg K.
AU - Shou, Yaping
AU - Singer, Robert H.
AU - Kuehl, W. Michael
N1 - Funding Information:
This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; and NIH grants CA83208 and EB2060 (R.H.S.). The authors would like to acknowledge Leslie Brents for technical contributions, Ana Gabrea for help in preparation of the manuscript, and also Keith Caldecott, James Haber, and Richard Kolodner for helpful discussions.
PY - 2009/3/1
Y1 - 2009/3/1
N2 - 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 ∼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.
AB - 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 ∼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.
KW - Cyclin D1
KW - IgH enhancer
KW - Karpas-620
KW - MYC
KW - Multiple myeloma
KW - Translocations
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UR - http://www.scopus.com/inward/citedby.url?scp=59149091389&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2008.11.010
DO - 10.1016/j.dnarep.2008.11.010
M3 - Article
C2 - 19064000
AN - SCOPUS:59149091389
SN - 1568-7864
VL - 8
SP - 330
EP - 335
JO - DNA Repair
JF - DNA Repair
IS - 3
ER -