{"entity":{"id":"chromoplexy","kind":"term","name":"Chromoplexy","aka":["chromoplectic rearrangement","chained rearrangements","punctuated evolution prostate genome","closed chains of rearrangement"],"tldr":"Instead of collecting damage one mutation at a time, a prostate cancer genome can be scrambled in a single burst: several chromosomes break at once and are stitched back together in a chain, knocking out several cancer genes in one event. It was discovered in prostate cancer and named there.","summary":"Chromoplexy is a pattern of interdependent DNA translocations and deletions that arise together rather than sequentially, forming chains that can involve several chromosomes and disrupt multiple cancer genes coordinately. Baca, Garraway and Rubin described and named it after whole-genome sequencing of 57 prostate tumours with matched normal tissue and modelling how the rearrangements they found could have arisen: translocations and deletions were abundant and highly interdependent, chromoplexy frequently accounted for the dysregulation of prostate cancer genes, and the modelling suggested it can derange a large amount of genome in relatively few events. Ordering the clonal hierarchy of those lesions charted a path of oncogenic events along which chromoplexy appeared to drive carcinogenesis.\n\nWhat it changed is the model of the disease. The classical picture of cancer as the gradual accumulation of point mutations does not describe prostate cancer, and chromoplexy is the main reason why. It is a model of punctuated evolution: long quiet periods interrupted by catastrophic rearrangement. It sits beside the other observation that makes prostate cancer unusual among common carcinomas, Grasso's finding of a mutation rate of only 2.00 per megabase even in lethal, heavily pre-treated castration-resistant disease, and Chung's real-world median tumour mutational burden of 2.6 mutations per megabase across 3,476 tumours. A structurally rearranged but point-mutationally quiet genome is why tumour mutational burden rarely qualifies prostate cancer for checkpoint immunotherapy, and why the archetypal prostate cancer lesion is a fusion, TMPRSS2-ERG, rather than a kinase mutation.\n\nIt is a model rather than a therapy. Chromoplexy is inferred from the pattern of rearrangements by modelling rather than observed as it happens, it was characterised in 57 mostly primary tumours so its frequency across the disease is not established, and no treatment follows from it. Its practical consequence is assay choice: whole-genome sequencing sees chained rearrangements and exome sequencing does not.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Chromoplexy","links":[{"label":"Baca et al., Cell 2013: punctuated evolution of prostate cancer genomes","url":"https://doi.org/10.1016/j.cell.2013.03.021"},{"label":"Grasso et al., Nature 2012: the mutational landscape of lethal castration-resistant prostate cancer","url":"https://doi.org/10.1038/nature11125"},{"label":"Chung et al., JCO Precision Oncology 2019: prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours","url":"https://doi.org/10.1200/po.18.00283"}],"tags":["gu","prostate-glossary"],"related":["paper-baca-punctuated-evolution-chromoplexy-cell-2013","paper-grasso-mutational-landscape-lethal-crpc-nature-2012","paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015","genome-wide-loss-of-heterozygosity"],"cancers":["prostate","prostate-high-risk","prostate-mcrpc"],"sections":["diagnostics","drug-discovery"],"technologies":["wes-wgs","ngs"],"targets":["erg","tmprss2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ngs","tmb","wes-wgs"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-undruggable-targets"],"keyPapers":["paper-baca-punctuated-evolution-chromoplexy-cell-2013","paper-grasso-mutational-landscape-lethal-crpc-nature-2012"],"journals":[],"dependsOn":[],"notes":["Chromoplexy is not chromothripsis. Chromothripsis is the shattering and haphazard reassembly of one chromosome or chromosome arm, producing many fragments and oscillating copy number. Chromoplexy is a chain of balanced or near-balanced rearrangements linking several chromosomes, with little copy number change, and was described in prostate cancer. Both are single-catastrophe models; they look different in the data and arise by different mechanisms.","The reason this word appears on a prostate page at all: it explains the shape of the disease's genome, which in turn explains two clinical facts a patient may meet. Immunotherapy generally does not work here, because there are too few mutations to make neoantigens. And the targeted drugs that do work are aimed at the hormone axis and at DNA repair, not at the kinases that dominate targeted therapy in other cancers."],"category":"Genomics & genetics"},"route":"/terms/chromoplexy/","neighbours":{"paper":[{"id":"paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","kind":"paper","name":"Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours","route":"/key-papers/paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019/"},{"id":"paper-baca-punctuated-evolution-chromoplexy-cell-2013","kind":"paper","name":"Punctuated evolution of prostate cancer genomes","route":"/key-papers/paper-baca-punctuated-evolution-chromoplexy-cell-2013/"},{"id":"paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015","kind":"paper","name":"The evolutionary history of lethal metastatic prostate cancer","route":"/key-papers/paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015/"},{"id":"paper-grasso-mutational-landscape-lethal-crpc-nature-2012","kind":"paper","name":"The mutational landscape of lethal castration-resistant prostate cancer","route":"/key-papers/paper-grasso-mutational-landscape-lethal-crpc-nature-2012/"}],"term":[{"id":"genome-wide-loss-of-heterozygosity","kind":"term","name":"Genome-wide loss of heterozygosity (gLOH)","route":"/terms/genome-wide-loss-of-heterozygosity/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"cancer":[{"id":"prostate-high-risk","kind":"cancer","name":"Localised prostate cancer, high and very high risk","route":"/cancers/prostate-high-risk/"},{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"drug-discovery","kind":"section","name":"Drug Discovery Platforms","route":"/fronts/drug-discovery/"}],"technology":[{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"erg","kind":"target","name":"ERG","route":"/targets/erg/"},{"id":"tmprss2","kind":"target","name":"TMPRSS2","route":"/targets/tmprss2/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}]}}