Mapping chromothripsis across human cancer cell lines reveals genome evolution and therapeutic vulnerabilities

Chromothripsis-like events are detected across 1,646 human cancer cell lines, with a higher prevalence than in primary tumors and ongoing emergence during culture propagation.

• Why it matters: Chromothripsis is linked to ~40% of primary tumors, but its occurrence and functional impact in cancer cell lines has been unknown.
• What they did: A copy-number–only pipeline was built to call chromothripsis-like events, then genomic and functional data were integrated to test drug sensitivities in chromothriptic versus non-chromothriptic cells.
• The result: Chromothriptic cells resist DNA damage-inducing agents but are highly sensitive to HDAC inhibitors, and isogenic models show HDACi synergistically sensitize chromothriptic cells to DNA damage-inducing agents.

AI summary of the abstract · may contain errors · not medical advice · read the paper.