Chromosomal instability reshapes cancer genomes one cell division at a time
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A study of 34 cancer cell lines and organoids, spanning high-grade serous ovarian carcinoma, pancreatic ductal adenocarcinoma, colorectal cancer, breast cancer and sarcoma, used single genome sequencing to measure how chromosomal instability (CIN) changes cancer genomes over time. The researchers found that each cell cycle produces one to five new copy number alterations (CNAs), largely distributed at random across the genome. Large CNAs were subject to negative selection, and whole genome duplication acutely raised CIN rates. Under chemotherapy selection pressure, genomes converged on recurrent therapy-associated CNAs even as CIN stayed high, suggesting treatment itself steers genome evolution. The findings, posted as a preprint, quantify CIN as a continuous force remaking tumor genomes rather than a one-time disruption.
Written by a model from the reports · updated 3 hours ago
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- biorxiv.orgPickChromosomal instability drives continual flux in cancer genomes
Using single genome sequencing across 34 cancer cell lines and organoids, researchers found that chromosomal instability (CIN) generates one to five new copy number alterations (CNAs) per cell cycle. The study covered high-grade serous ovarian carcinoma, pancreatic ductal adenocarcinoma, colorectal cancer, breast cancer and sarcoma. New CNAs were largely randomly distributed across the genome, large CNAs were under negative selection, and whole genome duplication acutely increased CIN rates. Under chemotherapy selection pressure, genomes evolved convergently towards recurrent therapy-associated CNAs while CIN remained high.
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