Spatial proximity of translocation-prone gene loci in human lymphomas

Nat Genet. 2003 Jul;34(3):287-91. doi: 10.1038/ng1177.


Cancer cells frequently have disease-specific chromosome rearrangements. It is poorly understood why translocations between chromosomes recur at specific breakpoints in the genome. Here we provide evidence that higher-order spatial genome organization is a contributing factor in the formation of recurrent translocations. We show that MYC, BCL and immunoglobulin loci, which are recurrently translocated in various B-cell lymphomas, are preferentially positioned in close spatial proximity relative to each other in normal B cells. Loci in spatial proximity are non-randomly positioned towards the nuclear interior in normal B cells. This locus proximity is the consequence of higher-order genome structure rather than a property of individual genes. Our results suggest that the formation of specific translocations in human lymphomas, and perhaps other tissues, is determined in part by higher-order spatial organization of the genome.

Publication types

  • Comparative Study

MeSH terms

  • DNA-Binding Proteins / genetics*
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain / genetics*
  • Genes, myc / genetics*
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • In Situ Hybridization, Fluorescence
  • Lymphoma, B-Cell / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, Transforming Growth Factor beta / genetics
  • Transcription Factors / genetics*
  • Translocation, Genetic / genetics*


  • DNA-Binding Proteins
  • Immunoglobulin Heavy Chains
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, Transforming Growth Factor beta
  • Transcription Factors