Telomeric fusion is a major cytogenetic aberration of giant cell tumors ofbone

Giant cell tumor of bone (GCT) is regarded as a rare primary bone neoplasm derived from stromal cells, which have the ability to recruit and harbor ma crophage and multinucleated osteoclast-like giant cells. Despite being ofte n considered benign, GCT is a problematic neoplasm in that it is aggressive , unpredictable and difficult to treat effectively. Cytogenetically GCT is characterised by a high frequency of telomeric fusion, a process which has been implicated in the production of chromosome instability and tumorigenes is. To extend our knowledge of the significance of telomere association in GCT, the cytogenetics of cell lines derived from spindle-shaped stromal-lik e mononuclear cells (the tumor cells) of GCT was investigated. Cell lines f rom three different patients showed telomeric association in all passages. The rate of telomeric association varied from line to line and from passage to passage, but there was no particular pattern to the variations. Many ot her cytogenetic abnormalities were seen as well as telomeric association, b ut these were rarely clonal. The nature of most of the other abnormalities seen, such as deleted chromosomes and chromosomes with additional unidentif iable material, was consistent with their being formed as a result of break age of the dicentric fused chromosomes at a telophase. chromosomes 13, 14 a nd 21 were most commonly involved in telomeric fusion. It appears that telo meric association persists in long-term cultures of GCT and is responsible for the accumulation of other associated cytogenetic aberrations. Telomeric reduction and telomerase activity may act as oncogenic events, promoting a nd sustaining the transformed GCT phenotype.