Mutability Dependence of Breast Cancer Metastasis and Latency to Recurrence.

Over 95% of breast cancer patients harbor metastasis-specific mutations in at least 10 pathways, with mutability-dependent mutations accumulating after dissemination to influence metastasis.

• Why it matters: Understanding when mutations occur during metastasis is crucial for developing targeted interventions and predicting metastatic latency, yet the timing and functional relevance of these mutations remain unclear.
• What they did: Genomic data from 662 paired and approximately 6,000 unpaired primary and metastatic tumors were analyzed, revealing that metastasis-specific mutations are often acquired post-dissemination, especially via APOBEC mutagenesis, and are dependent on metastatic site.
• The result: More than half of the variation in metastatic latency is explained by the timing of mutation acquisition within key pathways, supporting a model where mutations after dissemination drive metastatic outgrowth and influence latency duration.