Telomere Capture as a Frequent Mechanism for Stabilization of the Terminal Chromosomal Deletion Associated with Inverted Duplication

Abstract

We report 4 interstitial inverted duplications with associated terminal deletions (inv dup del) involving the short arms of chromosomes 5 and 8, and the long arm of chromosome 13 by microarray-based comparative genomic hybridization (aCGH) combined with chromosome banding (GTG banding) and fluorescence in situ hybridization (FISH) analyses. Formation of the intermediate dicentric chromosomes in 3 of them occurred through breakage-fusion-bridge cycle mechanism (U-type exchange mechanism) and in the fourth one it occurred through the mediation of the inverted low-copy repeats on chromosome 8p23.1. Two of these 4 inv dup del were confirmed and a third one was suspected to be associated with telomere capture for the healing of the terminal deletions. These findings indicate that a telomere capture mechanism is frequently used for stabilizing the broken chromosome ends in this type of genomic rearrangements. In addition, the inv dup del(13) represents the first observation of inv dup del on chromosome 13 in humans, the inv dup del(5) represents the first observation of inv dup del(5p) with an associated telomere capture, and unique features of the remaining two inv dup del(8p) were also discussed.