Chromoplexy

Chromoplexy refers to a class of complex DNA rearrangement observed in the genomes of cancer cells. This phenomenon was first identified in prostate cancer by whole genome sequencing of prostate tumors. Chromoplexy causes genetic material from one or more chromosomes to become scrambled as multiple strands of DNA are broken and ligated to each other in a new configuration. In prostate cancer, chromoplexy may cause multiple oncogenic events within a single cell cycle, providing a proliferative advantage to a (pre-)cancerous cell. Several oncogenic mutations in prostate cancer occur through chromoplexy, such as disruption of the tumor suppressor gene PTEN or creation of the TMPRSS2-ERG fusion gene. Chromoplexy refers to a class of complex DNA rearrangement observed in the genomes of cancer cells. This phenomenon was first identified in prostate cancer by whole genome sequencing of prostate tumors. Chromoplexy causes genetic material from one or more chromosomes to become scrambled as multiple strands of DNA are broken and ligated to each other in a new configuration. In prostate cancer, chromoplexy may cause multiple oncogenic events within a single cell cycle, providing a proliferative advantage to a (pre-)cancerous cell. Several oncogenic mutations in prostate cancer occur through chromoplexy, such as disruption of the tumor suppressor gene PTEN or creation of the TMPRSS2-ERG fusion gene. Chromplexy was originally inferred by statistically analyzing the location of DNA breaks across the genome. Its prevalence across cancers is not known, because only a few types of tumors have been analyzed for chromoplexy in the published literature. However, it was detected in the majority of 57 prostate tumors analyze and has been reported in non-small cell lung cancers, melanoma and head and neck squamous cell cancers. It has also been reported to generate the canonical gene fusion, EWSR1-FLI1 and EWSR1-ERG, in Ewing sarcoma. Along with chromothripsis, and break-fusion-bridge cycles, chromoplexy is an example of chromoanagenesis, a catch-all term for events that generate complex structural chromosomal abnormalities. The mechanism underlying complex rearrangements in chromoplexy has not been identified. A proposed model is that DNA is brought together in nuclear transcription hubs where genes across multiple chromosomes are co-regulated by transcription factors such as the Androgen receptor. This DNA may then sustain multiple transient breaks during transcription and sets of broken DNA ends may be ligated to one another in an incorrect configuration.