To the Editor:
Recently Chesi et al1 presented the characterization of 14q32 breakpoints in two t(11; 14)-bearing multiple myeloma cell lines, KMS12 and SK-MM2. In KMS12 the position of the 11q13 breakpoint could not be determined by polymerase chain reaction (PCR) screening of a YAC-contig extending 500 kb centromeric and 200 kb telomeric from the cyclin D1 gene. In the Blood issue of August 15, 1996 we reported the accurate mapping of breakpoints within the 11q13-/BCL1 region in mantle cell lymphoma by multicolor barcode fiber fluorescence in situ hybridization (FISH).2 Using this technique we have analyzed the KMS12 cell line with cosmid and P1 clones from 11q13/BCL1 and a contig of 14q32 cosmid and plasmid probes covering JH and the entire CH region. The results (Fig 1) show that the breakpoint on 11q13 is approximately 215 kb centromeric from the BCL1-MTC, or 330 kb centromeric from the cyclin D1 gene. Thus, the BCL1 breakpoint region is extended to at least 350 kb. The fact that the YAC contig screened by Chesi et al did not contain the breakpoint might be due to unstability of YACs cloned from the region centromeric from the BCL1MTC.3
The top panel shows the germline configuration of the 14q32 plasmid and cosmid probes. The second panel shows how 14q32 would look after VDJ recombination and class switching. The third and fourth panels show the reciprocal translocation products observed in KMS12 cells, while the bottom panel represents the germline configuration of the 11q13 cosmid and P1 probes. All probes are described in Vaandrager et al,2 except cosIg6,4 cCL11-505 (JCRF, Tokyo, Japan), the γ plasmid,5 and the α plasmid.6
The top panel shows the germline configuration of the 14q32 plasmid and cosmid probes. The second panel shows how 14q32 would look after VDJ recombination and class switching. The third and fourth panels show the reciprocal translocation products observed in KMS12 cells, while the bottom panel represents the germline configuration of the 11q13 cosmid and P1 probes. All probes are described in Vaandrager et al,2 except cosIg6,4 cCL11-505 (JCRF, Tokyo, Japan), the γ plasmid,5 and the α plasmid.6
To characterize the IgH constant region genes complex involved in the translocation, separate hybridizations were performed with γ- and α-specific plasmid probes and cosmids from JH-Sμ , in combination with 11q13 probes. The 14q+ chromosome contains, from breakpoint to centromere, two γ genes and one α gene, confirming the localization of the breakpoint in the switch-region of γ2. The 11q− chromosome contains only a few kilobases of sequence representing the JH-Sμ region (Fig 1). This suggests that γ2 class switch deletion has actually occurred. In conclusion, these data suggest that the observed overexpression of cyclin D1 in KMS12 may be caused by the presence of immunoglobulin sequences 330 kb centromeric from the cyclin D1 gene.
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