Structural instability of a transmissible end-to-end dicentric chromosome in a xeroderma pigmentosum fibroblast clone.

Cytogenetic analysis was performed in a fibroblast clone (XP9UV25) selected for anchorage-independent growth from an XP strain of normal origin and characterized by the presence of clonal chromosome rearrangements. A dicentric chromosome involving the 5p and 16q telomeric regions was observed in XP9UV25 cells at the fifth passage from colony isolation and at successive passages. The specific anomaly was present with increasing frequency (from 22 to 60% of mitoses) during culture propagation, undergoing rearrangements that gave rise to: 1) (5;16) dicentrics with deletions or duplications of the intercentromeric region; 2) homodicentrics for chromosomes 5 or 16, either end-to-end associations or rearranged; and 3) derivative 5p+ and 16q+ monocentric chromosomes. The frequency of other anomalies involving other chromosomes was negligible. These findings represent the first demonstration that a telomeric association leads to a variety of balanced and unbalanced chromosome rearrangements. These rearrangements may result from asymmetric interchanges between sister chromatids, "bridge-breakage-fusion" events during cell division, breakage and reunion of isochromatids, and breakage followed by healing of the ends. The type of anomaly and the sequence of karyotypic changes we observed in the XP9UV25 clone and their mechanisms of origin may be the same as those occurring during transformation from diploidy to aneuploidy in neoplastic cells.