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.
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 ( approximately 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.
Barbouti
Aikaterini
A
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
Stankiewicz
Pawel
P
Nusbaum
Chad
C
Cuomo
Christina
C
Cook
April
A
Höglund
Mattias
M
Johansson
Bertil
B
Hagemeijer
Anne
A
Park
Sung-Sup
SS
Mitelman
Felix
F
Lupski
James R
JR
Fioretos
Thoas
T
D001752:Blast Crisis / Q000235:genetics; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D018404:Isochromosomes / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid