Chromosomal 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.