A Compendium of Mutational Signatures of Environmental Agents

Whole-genome-sequencing (WGS) of human tumors has revealed distinct mutation patterns that hint at the causative origins of cancer. We examined mutational signatures in 324 WGS human-induced pluripotent stem cells exposed to 79 known or suspected environmental carcinogens. Forty-one yielded characteristic substitution mutational signatures. Some were similar to signatures found in human tumors. Additionally, six agents produced double-substitution signatures and eight produced indel signatures. Investigating mutation asymmetries across genome topography revealed fully functional mismatch and transcription-coupled repair pathways. DNA damage induced by environmental mutagens can be resolved by disparate repair…

• KC
  King’s College London
• WT
  Wellcome Trust

  Awards: C60100/A23916, 101126/B/13/Z, WT100183MA
• CR
  Cancer Research UK

  Awards: C60100/A23916, C313/A14329, A14329
• UO
  University of Cambridge
• KC
  King's College London