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The effects of mutational processes and selection on driver mutations across cancer types

Author

Listed:
  • Daniel Temko

    (Queen Mary University of London, Charterhouse Sq
    University College London
    University College London)

  • Ian P. M. Tomlinson

    (University of Birmingham)

  • Simone Severini

    (University College London
    Shanghai Jiao Tong University)

  • Benjamin Schuster-Böckler

    (University of Oxford)

  • Trevor A. Graham

    (Queen Mary University of London, Charterhouse Sq)

Abstract

Epidemiological evidence has long associated environmental mutagens with increased cancer risk. However, links between specific mutation-causing processes and the acquisition of individual driver mutations have remained obscure. Here we have used public cancer sequencing data from 11,336 cancers of various types to infer the independent effects of mutation and selection on the set of driver mutations in a cancer type. First, we detect associations between a range of mutational processes, including those linked to smoking, ageing, APOBEC and DNA mismatch repair (MMR) and the presence of key driver mutations across cancer types. Second, we quantify differential selection between well-known alternative driver mutations, including differences in selection between distinct mutant residues in the same gene. These results show that while mutational processes have a large role in determining which driver mutations are present in a cancer, the role of selection frequently dominates.

Suggested Citation

  • Daniel Temko & Ian P. M. Tomlinson & Simone Severini & Benjamin Schuster-Böckler & Trevor A. Graham, 2018. "The effects of mutational processes and selection on driver mutations across cancer types," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04208-6
    DOI: 10.1038/s41467-018-04208-6
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    Cited by:

    1. Andrey A. Yurchenko & Fatemeh Rajabi & Tirzah Braz-Petta & Hiva Fassihi & Alan Lehmann & Chikako Nishigori & Jinxin Wang & Ismael Padioleau & Konstantin Gunbin & Leonardo Panunzi & Fanny Morice-Picard, 2023. "Genomic mutation landscape of skin cancers from DNA repair-deficient xeroderma pigmentosum patients," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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