Proximity of Chromosomal Loci That Participate in Radiation-Induced Rearrangements in Human Cells
10.1126/science.290.5489.138
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

Rearrangements involving the RET gene are common in radiation-associated papillary thyroid cancer (PTC). The RET /PTC1 type of rearrangement is an inversion of chromosome 10 mediated by illegitimate recombination between the RET and the H4 genes, which are 30 megabases apart. Here we ask whether despite the great linear distance between them, RET and H4 recombination might be promoted by their proximity in the nucleus. We used two-color fluorescence in situ hybridization and three-dimensional microscopy to map the positions of the RET and H4 loci within interphase nuclei. At least one pair of RET and H4 was juxtaposed in 35% of normal human thyroid cells and in 21% of peripheral blood lymphocytes, but only in 6% of normal mammary epithelial cells. Spatial contiguity of RET and H4 may provide a structural basis for generation of RET /PTC1 rearrangement by allowing a single radiation track to produce a double-strand break in each gene at the same site in the nucleus.

Bibliography

Nikiforova, M. N., Stringer, J. R., Blough, R., Medvedovic, M., Fagin, J. A., & Nikiforov, Y. E. (2000). Proximity of Chromosomal Loci That Participate in Radiation-Induced Rearrangements in Human Cells. Science, 290(5489), 138–141.

Authors 6
  1. Marina N. Nikiforova (first)
  2. James R. Stringer (additional)
  3. Ruthann Blough (additional)
  4. Mario Medvedovic (additional)
  5. James A. Fagin (additional)
  6. Yuri E. Nikiforov (additional)
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  29. We thank H.-U. G. Weier and J. W. Gray for providing the P1 clones 29F6 RM10P013 and RMC10P016 and S. Heffelfinger and M. Stampfer for providing NME cells. Supported by a Thyroid Research Advisory Council Award from Knoll Pharmaceuticals (Y.E.N.) and in part by grants PO1 ES 05652-10 (J.R.S.) and CA 72597 (J.A.F.) from NIH. Dedicated to the memory of Tatiana Yevgenievna Strazdovskaya.
Dates
Type When
Created 23 years, 1 month ago (July 27, 2002, 5:53 a.m.)
Deposited 1 year, 7 months ago (Jan. 13, 2024, 5:19 a.m.)
Indexed 1 week, 6 days ago (Aug. 19, 2025, 6:14 a.m.)
Issued 24 years, 10 months ago (Oct. 6, 2000)
Published 24 years, 10 months ago (Oct. 6, 2000)
Published Print 24 years, 10 months ago (Oct. 6, 2000)
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@article{Nikiforova_2000, title={Proximity of Chromosomal Loci That Participate in Radiation-Induced Rearrangements in Human Cells}, volume={290}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.290.5489.138}, DOI={10.1126/science.290.5489.138}, number={5489}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Nikiforova, Marina N. and Stringer, James R. and Blough, Ruthann and Medvedovic, Mario and Fagin, James A. and Nikiforov, Yuri E.}, year={2000}, month=oct, pages={138–141} }