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Proximity of Chromosomal Loci That Participate in Radiation-Induced Rearrangements in Human Cells
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.
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Citations
Cited by
DNA double-strand breaks: signaling, repair and the cancer connection
Khanna, K. K., & Jackson, S. P. (2001) · Nature Genetics · doi:10.1038/85798 · Cited by 2,455
The impact of translocations and gene fusions on cancer causation
Mitelman, F., Johansson, B., & Mertens, F. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2091 · Cited by 1,400
Biologic and Clinical Perspectives on Thyroid Cancer
Fagin, J. A., & Wells, S. A. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1501993 · Cited by 990
Self-citationPathogenetic mechanisms in thyroid follicular-cell neoplasia
Kondo, T., Ezzat, S., & Asa, S. L. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1836 · Cited by 893
Lin, C., Yang, L., Tanasa, B., Hutt, K., Ju, B.-G., Ohgi, K. A., Zhang, J., Rose, D. W., Fu, X.-D., Glass, C. K., et al. (2009) · Cell · doi:10.1016/j.cell.2009.11.030 · Cited by 576
Metadata
- Authors
- Nikiforova, M. N., Stringer, J. R., Blough, R., Medvedovic, M., Fagin, J. A., & Nikiforov, Y. E.
- Venue
- Science
- Published
- 2000-10-06
- Volume
- 290
- Issue
- 5489
- Pages
- 138-141
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1963634449
- Cited by
- 468
- References
- 0
- FWCI
- 21.39
- Type
- journal article
- Language
- en
- Open access
- closed
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- 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. https://doi.org/10.1126/science.290.5489.138
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