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Conformational differences in the 3-D nanostructure of the immunoglobulin heavy-chain locus, a hotspot of chromosomal translocations in B lymphocytes. Cancer Genet Cytogenet 2001 Jun;127(2):168-73

Date

06/27/2001

Pubmed ID

11425458

DOI

10.1016/s0165-4608(01)00455-1

Scopus ID

2-s2.0-0034968320   21 Citations

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, C mu, and the 3' most IgH gene, C alpha, 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 C mu/C alpha distance (genomic distance approximately 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 C mu/C alpha 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.

Author List

Esa A, Coleman AE, Edelmann P, Silva S, Cremer CG, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
B-Lymphocytes
Chromosome Mapping
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 15
DNA
Genes, Immunoglobulin
Humans
Immunoglobulin Heavy Chains
In Situ Hybridization, Fluorescence
Leukemia, B-Cell
Lymphoma, B-Cell
Mice
Multigene Family
Nucleic Acid Conformation
Translocation, Genetic