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Most cancers have the wrong number of chromosomes and keep shuffling them at every division. This chaos fuels evolution and drug resistance, but it also stresses the cell and can trigger immune alarms, a double edge that researchers are trying to exploit.
Chromosomal instability (CIN) arises from mitotic errors, whole-genome doubling, replication stress, and centrosome amplification; it produces aneuploidy, micronuclei, chromothripsis, and ecDNA (extrachromosomal oncogene amplicons). Consequences: intratumour heterogeneity and rapid adaptation (TRACERx), cytosolic DNA that activates cGAS-STING (immunogenic in bursts, tolerated chronically via non-canonical NF-κB), and proteotoxic and metabolic stress that creates dependencies (KIF18A, spindle assembly checkpoint, BCL-XL). CIN is a poor-prognosis marker across cancers; ecDNA drives resistance to targeted therapy in glioblastoma and others.
Chromosomal instability is a library that reshuffles and duplicates random shelves every night. Most rearrangements are useless, some ruin the building, but occasionally one yields a book the librarian needs to survive a new rule, and the mess itself keeps the fire alarms twitching.
Relapse after surgery is driven by particular subclones that can be identified in the primary tumour and tracked in blood, which argues for evolution-aware adjuvant strategies. The pollution finding reframes carcinogenesis: some agents promote already-mutant cells rather than causing mutations.
It separates two explanations that are usually run together. Some of the difference in prostate cancer outcomes by race is in the tumour genome and persists when access to the same centre is held constant, and some of it tracks with income rather than with ancestry, so equalising access alone would not eliminate the gap.
Lung cancer in never-smokers is not smokers' lung cancer with the smoking removed; it is a different set of diseases with a different clock. The slow-growing piano subtype in particular is the argument that a screening test aimed at never-smokers would need to look for something other than what low-dose computed tomography was built to find.
It explains why single-sample classifiers disagree on about one tumour in eight and why KRAS allelic imbalance and GATA6 copy number are being read alongside expression.
One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
It shows that the commonest driver event in advanced prostate cancer is invisible to the panels used to test for it, and that the shape of the structural damage in a genome tells you which repair pathway failed, which is information a mutation list does not carry.
It is the reason a prostate cancer fusion frequency quoted without an ancestry is unsafe. In this cohort the founder event that defines almost half of Western tumours is uncommon, and the fusion-negative, CHD1-deleted route dominates instead.
It supplies the biological reason for treating a BRCA2 carrier's localised disease aggressively rather than watching it, and it settles a long-standing pathology question by showing that intraductal carcinoma and the adjacent invasive tumour are the same clone rather than two separate processes.
Shares Genomic and evolutionary classification of lung cancer in never smokers, The Francis Crick Institute, Theories of cancer: how the ideas connect, Clonal evolution & minimal residual disease and the tag mechanism.
Shares The Francis Crick Institute, Theories of cancer: how the ideas connect, Stanford Health Care / Stanford Cancer Institute, Clonal evolution & minimal residual disease and the tag mechanism.
Shares The Francis Crick Institute, Theories of cancer: how the ideas connect, MYC, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares DNA replication stress, Stanford Health Care / Stanford Cancer Institute, Pancreatic ductal adenocarcinoma, Colorectal cancer and the tag mechanism.
Shares Stanford Health Care / Stanford Cancer Institute, Memorial Sloan Kettering Cancer Center, Pancreatic ductal adenocarcinoma, Prostate cancer and the tag mechanism.
Shares CDKN2A, p53 / RB / cell-cycle checkpoint, Memorial Sloan Kettering Cancer Center, TP53 and the tag mechanism.
Shares MYC, p53 / RB / cell-cycle checkpoint, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares Theories of cancer: how the ideas connect, Clonal evolution & minimal residual disease, Memorial Sloan Kettering Cancer Center, TP53 and the tag mechanism.