The structure and dynamics of ring chromosomes in human neoplastic and non-neoplastic cells

Acquired ring chromosomes have been found in most types of human neoplasia, with a frequency approaching 10% in malignant mesenchymal rumours. In this study, the composition and dynamics of ring chromosomes were analysed in e ight cases of acute myelogenous leukaemia, 17 solid rumours, and five cases with constitutional rings. Chromosomal banding and fluorescence in situ hy bridisation were performed to determine the content and the structural hete rogeneity of the rings. Telomeric repeats were detected using peptide nucle ic acid probes or primed in situ labelling, whereas centromeric activity wa s evaluated by detection of kinetochore proteins. Mitotic instability was a ssessed by the frequency of anaphase bridges. The results suggest that huma n ring chromosomes can be structurally and functionally divided into two ca tegories. In the first of these, size variation is minimal and rearrangemen t at cell division is uncommon. The majority of such rings contain subtelom eric sequences. Constitutional ring chromosomes and most rings in leukaemia s belong to this group, whereas only a few mesenchymal tumours exhibit ring s of this type, The second category consists of rings with amplified sequen ces, primarily from chromosome 12, characteristically occurring in atypical lipomatous rumours and other subtypes of low or borderline malignant mesen chymal neoplasms. Variation in size and number is extensive, and breakage-f usion-bridge events occur at a high frequency. Abnormalities in pericentrom eric sequences are common and, in some cases, kinetochores assemble in the absence of alphoid DNA. We conclude that it is not only the ring structure per se or the neoplastic nature of the host cell that determines ring insta bility, but probably also the functional role of the genes carried in the r ing.