Chromoplexy: A Pathway to Genomic Complexity and Cancer Development

Chromoplexy is a phenomenon of complex genome rearrangement, occurring during a single cell event and characterized by the formation of chain rearrangements affecting multiple chromosomes. Unlike other genomic rearrangements such as chromothripsis, which involves a single chromosome, chromoplexy affects several chromosomes at once, creating patterns of complex, balanced translocations, and leading to the formation of fusion genes and the simultaneous disruption of several genes. Chromoplexy was first identified in prostate cancers, but it is now observed in various cancers where gene fusions take place. The precise mechanisms behind chromoplexy remain under investigation. The occurrence of these rearrangements follows multiple double-stranded breaks that appear to occur in certain regions or during particular genome configurations (open chromatin, active transcription area), and which lead to an intricate series of inter- and intra-chromosomal translocations and deletions without significant alterations in the number of copies. Although chromoplexy is considered a very early event in oncogenesis, the phenomenon can be repeated and can constitute a mechanism of clonal tumor progression. The occurrence of chromoplexy supports the equilibrium model punctuated by tumor evolution, characterized by periods of relative stability punctuated by sudden and rapid periods of radical genomic changes.