High burden and pervasive positive selection of somatic mutations in normal human skin

How somatic mutations accumulate in normal cells is central to understanding cancer development but is poorly understood. We performed ultradeep sequencing of 74 cancer genes in small (0.8 to 4.7 square millimeters) biopsies of normal skin. Across 234 biopsies of sun-exposed eyelid epidermis from four individuals, the burden of somatic mutations averaged two to six mutations per megabase per cell, similar to that seen in many cancers, and exhibited characteristic signatures of exposure to ultraviolet light. Remarkably, multiple cancer genes are under strong positive selection even in physiologically normal skin, including most of the key drivers of cutaneous squamous cell carcinomas. Positively selected…

• EM
  European Molecular Biology Organization

  Award: 1287-2012
• W
  Wellcome

  Award: 077012/Z/05/Z
• CR
  Cancer Research UK

  Award: C609/A17257
• MR
  Medical Research Council