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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.
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.
What 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.
It 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.
In plain words · ERG (Transcriptional regulator ERG) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Sarcomas, Prostate cancer, Non-Hodgkin lymphoma and 4 more.
Showing the target this term concerns: ERG.
What a prostate cancer sequencing report looks like in practice, and the numerical basis for two clinical rules: do not expect checkpoint immunotherapy to work unless the tumour is mismatch repair deficient, and do not treat a CDK12 alteration as if it were a BRCA alteration.
Metastatic prostate cancer is a communicating population, not a set of independent colonies, which is an argument for treating the whole body rather than chasing individual deposits, and an argument that resistance to androgen receptor drugs will emerge in several places at once because it emerges convergently.
A different picture of how a cancer genome is built, and one that explains why prostate cancer has few point mutations and a great deal of structural damage. It is also why whole-genome rather than exome sequencing is the right assay for this disease.
The explanation for why prostate cancer has so few targeted drugs outside the hormone axis and the DNA-repair genes: it is a quiet genome with structural rather than point-mutational damage, and the recurrent changes sit in the machinery that reads DNA rather than in kinases.
Shares Tumour heterogeneity and clonal evolution, Metastatic castration-resistant prostate cancer, Prostate cancer and the tags gu, prostate-glossary.
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Shares Localised prostate cancer, high and very high risk, Prostate cancer and the tags gu, prostate-glossary.
Shares Localised prostate cancer, high and very high risk, Prostate cancer and the tags gu, prostate-glossary.
Shares Localised prostate cancer, high and very high risk, Prostate cancer and the tags gu, prostate-glossary.
Shares Localised prostate cancer, high and very high risk, Prostate cancer and the tags gu, prostate-glossary.
Shares Localised prostate cancer, high and very high risk, Prostate cancer and the tags gu, prostate-glossary.
Shares Localised prostate cancer, high and very high risk, Prostate cancer and the tags gu, prostate-glossary.