Genomic instability in multiple myeloma: Evidence for jumping segmental duplications of chromosome arm Iq

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by complex karyotypes and chromosome I instability at the cytogenetic level. Chromosome I instability generally involves partial duplications, whole-arm translocations, or jumping translocations of Iq, identified by G-banding. To characterize this instability further, we performed spectral karyotyping and fluorescence in situ hybridization with probes for satII/III (Iq12), BCL9 (Iq2I), and UR (Iq2I) on the karyotypes of 44 patients with known Iq aberrations. In eight patients, segmental duplication of Iq12-21 and adjacent bands occurred on nonhomologous chromosomes. In five cases, the Iq first jumped to a nonhomologous chromosome, after which the Iq12-21 segment again duplicated itself 1-3 times. In three other cases, segmental duplications occurred after the Iq first jumped to a nonhomologous chromosome, where the proximal adjacent nonhomologous chromosome segment was duplicated prior to the Iq jumping or inserting itself into a new location. These cases demonstrate that satII/III DNA sequences are not only associated not only with the duplication of adjacent distal chromosome segments after translocation, but are also associated with the duplication and jumping/insertion of proximal nonhomologous chromosome segments. We have designated this type of instability as a jumping segmental duplication. (C) 2004 Wiley-Liss, Inc.