Cancer and neoplasms

The evolving cancer genome

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Metastatic disease causes most deaths from cancer but how the cancer genome evolves during the progression from primary to secondary disease remains an important unanswered question. Reporting in Nature, Martínez-Jiménez et al. re-analyzed whole-genome sequences from 7,108 tumors across 23 cancer types comprising untreated primary tumors and (unmatched) treated secondary tumors. Their results showed that patterns of genomic evolution were highly dependent on cancer type and were often related to treatment. Broadly, metastatic tumors showed higher levels of clonality, were enriched for structural variants, and displayed deep mutational footprints of previous treatments. However, only a handful of tumor types showed significant genomic differences between the primary and secondary settings. Notably, the authors also noticed an enrichment of the clock-like mutational signature SBS1 in metastatic lesions from certain cancer types and they speculate that this might be due to enhanced rates of cell division in advanced disease. Large-scale analyses of primary and metastatic tumors are crucial to understand how genome evolution propels cancer progression, and to determine pan-cancer and tumor-specific mechanisms that may be harnessed for therapeutic benefit.

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  1. Nature Genetics https://www.nature.com/ng/

    Safia Danovi

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  1. Safia Danovi
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Danovi, S. The evolving cancer genome.
Nat Genet 55, 1082 (2023). https://doi.org/10.1038/s41588-023-01457-0

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  • Published: 12 July 2023

  • Issue Date: July 2023

  • DOI: https://doi.org/10.1038/s41588-023-01457-0

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