Copyright © 2004 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 74, Issue 1, 1-10, 1 January 2004
doi:10.1086/380648
The Breakpoint Region of the Most Common Isochromosome, i(17q), in Human Neoplasia Is Characterized by a Complex Genomic Architecture with Large, Palindromic, Low-Copy Repeats
Aikaterini Barbouti1, *, Pawel Stankiewicz2, *, Chad Nusbaum5, Christina Cuomo5, April Cook5, Mattias Höglund1, Bertil Johansson1, Anne Hagemeijer6, Sung-Sup Park2, †, Felix Mitelman1, James R. Lupski2, 3, 4 and Thoas Fioretos1, 
, 
1 Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
2 Department of Molecular and Human Genetics, Houston
3 Department of Pediatrics, Baylor College of Medicine, Houston
4 Department of Texas Children’s Hospital, Houston
5 Whitehead Institute for Biomedical Research/Massachusetts Institute of Technology, Center for Genome Research, Cambridge, MA
6 Department of Human Genetics, University of Leuven, Leuven, Belgium
Address for correspondence and reprints: Dr. Thoas Fioretos, Department of Clinical Genetics, Lund University Hospital, Lund, SE-22185, Sweden* These authors contributed equally to this work.
† Present affiliation: Department of Clinical Pathology, Seoul National University Hospital, Seoul, South Korea.
Abstract
Although a great deal of information has accumulated regarding the mechanisms underlying constitutional DNA rearrangements associated with inherited disorders, virtually nothing is known about the molecular processes involved in acquired neoplasia-associated chromosomal rearrangements. Isochromosome 17q, or “i(17q),” is one of the most common structural abnormalities observed in human neoplasms. We previously identified a breakpoint cluster region for i(17q) formation in 17p11.2 and hypothesized that genome architectural features could be responsible for this clustering. To address this hypothesis, we precisely mapped the i(17q) breakpoints in 11 patients with different hematologic malignancies and determined the genomic structure of the involved region. Our results reveal a complex genomic architecture in the i(17q) breakpoint cluster region, characterized by large (∼38–49-kb), palindromic, low-copy repeats, strongly suggesting that somatic rearrangements are not random events but rather reflect susceptibilities due to the genomic structure.
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