Jumping translocations of 1q12 in multiple myeloma: a novel mechanism for deletion of 17p in cytogenetically defined high-risk disease

Blood. 2014 Apr 17;123(16):2504-12. doi: 10.1182/blood-2013-12-546077. Epub 2014 Feb 4.


Multiple myeloma (MM) is a B-cell malignancy driven in part by increasing copy number alterations (CNAs) during disease progression. Prognostically significant CNAs accumulate during clonal evolution and include gains of 1q21 and deletions of 17p, among others. Unfortunately, the mechanisms underlying the accumulation of CNAs and resulting subclonal heterogeneity in high-risk MM are poorly understood. To investigate the impact of jumping translocations of 1q12 (JT1q12) on receptor chromosomes (RCs) and subsequent clonal evolution, we analyzed specimens from 86 patients selected for unbalanced 1q12 aberrations by G-banding. Utilizing spectral karyotyping and locus-specific fluorescence in situ hybridization, we identified 10 patients with unexpected focal amplifications of an RC that subsequently translocated as part of a sequential JT1q12 to one or more additional RCs. Four patients exhibited amplification and translocation of 8q24 (MYC), 3 showed amplification of 16q11, and 1 each displayed amplification of 18q21.3 (BCL2), 18q23, or 4p16 (FGFR3). Unexpectedly, in 6 of 14 patients with the combination of the t(4;14) and deletion of 17p, we identified the loss of 17p as resulting from a JT1q12. Here, we provide evidence that the JT1q12 is a mechanism for the simultaneous gain of 1q21 and deletion of 17p in cytogenetically defined high-risk disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 1 / genetics*
  • Chromosomes, Human, Pair 17 / genetics*
  • Cytogenetic Analysis
  • Disease Progression
  • Humans
  • In Situ Hybridization, Fluorescence
  • Interspersed Repetitive Sequences
  • Karyotype
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / pathology
  • Risk
  • Translocation, Genetic*