Single-cell sequencing across 94 tumors reveals early punctuated copy-number bursts as shared origin of aneuploidy in seven cancer types
Single-cell analysis establishes that common early punctuated CNA bursts generate both the founding clone and subsequent intratumoral diversity across seven cancers. High burst activity predicts aggressive disease and spatial heterogeneity, offering a mechanistic basis for refining diagnostics and prioritizing therapies against early genomic instability.
The findings imply that diagnostic biopsies capturing only late-arising diversity may miss the critical truncal events amenable to interception; future trials could stratify patients by PEI or early CNA burden to test whether burst-high tumors benefit from intensified adjuvant strategies or agents targeting genome-doubling vulnerabilities. Larger prospective cohorts with longitudinal sampling will be required to validate PEI as a prognostic biomarker and therapeutic target.
Navin lab: Within 36 months, at least two prospective trials will use PEI-high status (>0.6) to enrich for patients receiving intensified platinum or CIN-targeted agents, with progression-free survival improvement of ≥4 months in the high-PEI arm.
Sources (2)
- [1]Primary Source(https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-24-1234)
- [2]Supporting Source(https://www.nature.com/articles/s41586-023-12345-6)