High burden and pervasive positive selection of somatic mutations in normal human skin
Iñigo Martincorena, Amit Roshan, Moritz Gerstung, Peter Ellis, Peter Van Loo, Stuart McLaren, David C. Wedge, Anthony Fullam, Ludmil B. Alexandrov, Jose M. Tubio, Lucy Stebbings, Andrew Menzies, Sara Widaa, Michael R. Stratton, Philip H. Jones, Peter J. Campbell- Multidisciplinary
Normal skin's curiously abnormal genome
Within every tumor, a battle is being waged. As individual tumor cells acquire new mutations that promote their survival and growth, they clonally expand at the expense of tumor cells that are “less fit.” Martincorena et al. sequenced 234 biopsies of sun-exposed but physiologically normal skin from four individuals (see the Perspective by Brash). They found a surprisingly high burden of mutations, higher than that of many tumors. Many of the mutations known to drive the growth of cutaneous squamous cell carcinomas were already under strong positive selection. More than a quarter of normal skin cells carried a driver mutation, and every square centimeter of skin contained hundreds of competing mutant clones.
Science
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