Metastatic Cancer Evolves Through Genetic Complexity

Strategic Insights -

Researchers from Memorial Sloan Kettering Cancer Center (MSK) and Weill Cornell Medicine have discovered that when cancer spreads to new sites throughout the body, it undergoes changes that increase its genetic complexity. This study provides fresh insights into the evolution of cancers during metastasis, which could aid in developing more effective treatment strategies. The team examined the genomic profiles of over 3,700 patients across 24 cancer types, revealing that metastatic tumors tend to accumulate more copy-number alterations (CNAs) than mutations. This finding has significant implications for the development of therapies that target genetic instability in these highly altered cells.

Key Takeaways:

  • Metastatic cancer evolves through genetic complexity, with tumors accumulating more copy-number alterations (CNAs) than mutations.
  • The study analyzed the genomic profiles of over 3,700 patients across 24 cancer types, using the MSK-IMPACT tumor sequencing test.
  • Whole-genome duplication, or the doubling of the entire set of chromosomes in a cancer cell, was the most common genetic event during metastasis, occurring in nearly one-third of patients.
  • CNAs, but not mutations, were commonly emerging when tumors metastasized, suggesting that CNAs are a key driver of metastatic progression.
  • The team found that CNAs made tumors resistant to immunotherapy, while mutations made tumors more susceptible to treatment.
  • Understanding these key genomic differences between primary and metastatic tumors is vital for clinical care, as biomarkers like CNAs and tumor mutational burden are increasingly used by clinicians to inform decision-making.

Statistics:

  • Over 3,700 patients across 24 cancer types were examined in the study.
  • The MSK-IMPACT tumor sequencing test was used to profile the genomic profiles of the patients.
  • Whole-genome duplication occurred in nearly one-third of patients during metastasis.
  • CNAs were commonly emerging at a rate of [statistics not explicitly stated in the source].
  • CNAs made tumors resistant to immunotherapy in [percentage] of cases.

Sources:

  • VerticalNews Health, "Study Reveals Mutational and Copy Number Evolution in Tumors During Metastatic Dissemination"
  • Nature Genetics, Longitudinal and multisite sampling reveals mutational and copy number evolution in tumors during metastatic dissemination, DOI: 10.1038/s41588-025-02204-3
  • MSK-IMPACT, a foundation for MSK's clinical precision oncology enterprise that has performed genomic profiling of 100,000 patients as part of their clinical care.