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Proximity of Chromosomal Loci That Participate in Radiation-Induced Rearrangements in Human Cells
Marina N. Nikiforova,12James
R. Stringer,3Ruthann Blough,5Mario Medvedovic,4James A. Fagin,2Yuri E. Nikiforov1*
Rearrangements involving the RET gene are common in
radiation-associated papillary thyroid cancer (PTC). The
RET/PTC1 typeof rearrangement is an inversion of chromosome
10 mediated byillegitimate recombination between the RET
and the H4 genes, whichare 30 megabases apart. Here we ask
whether despite the greatlinear distance between them, RET
and H4 recombination might bepromoted by their proximity in
the nucleus. We used two-colorfluorescence in situ hybridization and
three-dimensional microscopyto map the positions of the RET
and H4 loci within interphasenuclei. 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 contiguityof
RET and H4 may provide a structural basis for
generation ofRET/PTC1 rearrangement by allowing a single
radiation track toproduce a double-strand break in each gene at the
same site inthe nucleus.
1 Department of Pathology and Laboratory
Medicine,
2 Division of Endocrinology and
Metabolism,
3 Department of Molecular Genetics, and
4 Center for Biostatistical Services, University
of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
5 Cytogenetics Laboratory, Division of Human
Genetics, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
*
To whom correspondence should be addressed. E-mail:
Yuri.Nikiforov{at}uc.edu
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PERSPECTIVES
John R. K. Savage (6 October 2000) Science290 (5489), 62.
[DOI: 10.1126/science.290.5489.62] |Summary »|Full Text »
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