Nature Genetics34, 287 - 291 (2003)
Published online: 15 June 2003; | doi:10.1038/ng1177
Spatial proximity of translocation-prone gene loci in human lymphomas
Jeffrey J Roix1, Philip G McQueen2, Peter J Munson2, Luis A Parada1
& Tom Misteli1
1
National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
2
Mathematical and Statistical Laboratory, Division of Computational Bioscience, Center for Information Technology; National Institutes of Health, Bethesda, Maryland 20892, USA.
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.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
