Journal article
Conformational differences in the 3-D nanostructure of the immunoglobulin heavy-chain locus, a hotspot of chromosomal translocations in B lymphocytes
Cancer genetics and cytogenetics, Vol.127(2), pp.168-173
2001
DOI: 10.1016/S0165-4608(01)00455-1
PMID: 11425458
Abstract
Spectral precision distance microscopy was utilized to detect small but nonetheless consistently present conformational differences between the immunoglobulin heavy-chain gene clusters (IgH) that reside on the two chromosome 12 homologues in all diploid cells of the mouse. The euclidian distance (i.e., the mean arithmetic three-dimensional [3-D] distance) between the 5′ most IgH gene, Cμ, and the 3′ most IgH gene, Cα, was used as the indicator to define the co-presence of a condensed IgH domain and a relaxed IgH domain in the same cell. In normal and malignant B cells in which IgH is actively rearranged and transcribed, the Cμ/Cα distance (genomic distance ∼180 kb) was found to range from 87.5 to 121 nm on the condensed IgH domain and from 154 to 207 nm on the relaxed IgH domain. In non-B cells (fibroblasts, neutrophils, and macrophages), in which IgH is inactive, the Cμ/Cα distance was found to range from 136 to 154 nm on the condensed IgH domain and from 250 to 292 nm on the related IgH domain. These results suggested that conformational differences that may predispose the relaxed IgH domain for illegitimate genetic recombinations, such as chromosomal translocations, are likely to exist in many cell types, including B cells. However, in B lymphocytes this structural predisposition may conspire with the lineage-specific ability to activate proto-oncogenes (after juxtaposition to IgH) to positively affect the preferential involvement of the relaxed IgH domain in chromosomal translocations. Additional studies are warranted to validate this working hypothesis.
Details
- Title: Subtitle
- Conformational differences in the 3-D nanostructure of the immunoglobulin heavy-chain locus, a hotspot of chromosomal translocations in B lymphocytes
- Creators
- Arif Esa - Applied Optics and Information Processing, Kirchhoff Institute for Physics, University of Heidelberg, Heidelberg, GermanyAllen E Coleman - Laboratory of Genetics, Division of Basic Sciences, NCI, Building 37, Room 2B10, Bethesda, MD 20892-4255, USAPeter Edelmann - Applied Optics and Information Processing, Kirchhoff Institute for Physics, University of Heidelberg, Heidelberg, GermanySantiago Silva - MTC, Karolinska Institute, Stockholm, SwedenChristoph G Cremer - Applied Optics and Information Processing, Kirchhoff Institute for Physics, University of Heidelberg, Heidelberg, GermanySiegfried Janz - Laboratory of Genetics, Division of Basic Sciences, NCI, Building 37, Room 2B10, Bethesda, MD 20892-4255, USA
- Resource Type
- Journal article
- Publication Details
- Cancer genetics and cytogenetics, Vol.127(2), pp.168-173
- Publisher
- Elsevier Inc
- DOI
- 10.1016/S0165-4608(01)00455-1
- PMID
- 11425458
- ISSN
- 0165-4608
- eISSN
- 1873-4456
- Language
- English
- Date published
- 2001
- Academic Unit
- Pathology
- Record Identifier
- 9984083860002771
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