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Nat Genet. 2003 Jul;34(3):287-91.

Spatial proximity of translocation-prone gene loci in human lymphomas.

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

Abstract

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.

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PMID:
12808455
[PubMed - indexed for MEDLINE]
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