Overview

• Metastatic tumors exhibit a substantially higher burden of copy-number alterations than point mutations, highlighting chromosomal instability as a key evolutionary driver.
• Whole-genome doubling emerged in roughly one-third of metastatic cases, creating genetic redundancy that boosts tumor adaptability and treatment resilience.
• Researchers analyzed over 8,000 tumor samples from 3,732 patients across 24 cancer types, making this the most extensive paired primary-and-metastasis genomic study to date.
• High copy-number alteration loads correlate with poorer survival and reduced response to checkpoint inhibitors, signaling limits of current immunotherapy biomarkers.
• Authors recommend developing therapies that disrupt copy-number changes and genome-doubling mechanisms to improve durable responses in advanced cancer.