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Alu elements are short, ∼300-bp stretches of DNA and are the most abundant repetitive elements in the human genome. A large number of chromosomal rearrangements mediated by Alu-Alu recombination have been reported in germline cells, but only a few in somatic cells. Cancer development is frequently accompanied by various chromosomal rearrangements including gene amplification. To explore an involvement of Alu-Alu fusion in gene amplification events, we determined 20 junction site sequences of 5 highly amplified regions in 4 cancer cell lines. The amplified regions exhibited a common copy number profile: a stair-like increase with multiple segments, which is implicated in the breakage-fusion-bridge (BFB) cycle-mediated amplification. All of the sequences determined were characterized as head-to-head or tail-to-tail fusion of sequences separated by 1-5 kb in the genome sequence. Of these, 4 junction site sequences were identified as Alu-Alu fusions between inverted, paired Alu elements with relatively long overlapping sequences of 17, 21, 22, and 24 bp. Together with genome mapping data of Alu elements, these findings suggest that when breakages occur at or near inverted, paired Alu elements in the process of BFB cycle-mediated amplification, sequence homology of Alu elements is frequently used to repair the broken ends.

Alu-Alu Fusion Sequences Identified at Junction Sites of Copy Number Amplified Regions in Cancer Cell Lines