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Spatial proximity of translocation-prone gene loci in human lymphomas

Nature Genetics volume 34, pages 287–291 (2003)Cite this article

Abstract

Cancer cells frequently have disease-specific chromosome rearrangements1,2,3,4. 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.

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Figure 1: Non-random radial positioning of gene loci.
Figure 2: Spatial proximity of translocation-prone oncogene loci.
Figure 3: Close locus pairs are distributed non-randomly.
Figure 4: Relational topology of gene loci is determined by higher-order genome organization.

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Authors and Affiliations

  1. National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Jeffrey J Roix, Luis A Parada & Tom Misteli

  2. Mathematical and Statistical Laboratory, Division of Computational Bioscience, Center for Information Technology,

    Philip G McQueen & Peter J Munson

  3. National Institutes of Health, Bethesda, 20892, Maryland, USA

    Philip G McQueen & Peter J Munson

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  1. Jeffrey J Roix
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Correspondence to Tom Misteli.

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Roix, J., McQueen, P., Munson, P. et al. Spatial proximity of translocation-prone gene loci in human lymphomas. Nat Genet 34, 287–291 (2003). https://doi.org/10.1038/ng1177

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