Translocation t(11;14) in multiple myeloma: Analysis of translocation breakpoints on der(11) and der(14) chromosomes suggests complex molecular mechanisms of recombination.

Abstract

We describe the characterization of the genomic DNA breakpoints of two multiple myeloma (MM) patients with t(11;14). IGH translocation events are present in many MM tumors, and it is proposed that they occur early in the pathogenesis, based on the assumption that the translocations are simple reciprocal events mediated by errors in class-switch recombination (CSR). We provide evidence from two patients that the translocation event can be more complex, with DNA from chromosome band 11q13 joined to apparently already recombined hybrid (Smu/Sgamma) switch region sequences. In one case, there was also evidence that a further rearrangement had occurred at the t(11;14) recombination site, resulting in an inversion of 40 bp of the 5'Smu flanking sequence. This suggests that primary IGH arrangements in MM may be more complex than previous myeloma models have suggested, but that they essentially occur through illegitimate CSR events.