The evolutionary history of 2,658 cancers

PCAWG Evolution & Heterogeneity Working Group, PCAWG Consortium, Moritz Gerstung, Clemency Jolly, Ignaty Leshchiner

    Tutkimustuotos: ArtikkeliScientificvertaisarvioitu

    558 Sitaatiot (Scopus)

    Abstrakti

    Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.

    AlkuperäiskieliEnglanti
    Sivut122-128
    Sivumäärä7
    JulkaisuNature
    Vuosikerta578
    Numero7793
    DOI - pysyväislinkit
    TilaJulkaistu - 6 helmik. 2020
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

    !!ASJC Scopus subject areas

    • General

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