Signatures of mutational processes in human cancer

Research output: Contribution to journalArticle


All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.


  • Ludmil B. Alexandrov
  • Serena Nik-Zainal
  • David C. Wedge
  • Samuel A. J. R. Aparicio
  • Sam Behjati
  • Andrew V. Biankin
  • Graham R. Bignell
  • Niccolo Bolli
  • Anne-Lise Borresen-Dale
  • Sandrine Boyault
  • Birgit Burkhardt
  • Adam P. Butler
  • Carlos Caldas
  • Helen R. Davies
  • Christine Desmedt
  • Roland Eils
  • Jorunn Erla Eyfjord
  • John A. Foekens
  • Mel Greaves
  • Fumie Hosoda
  • Barbara Hutter
  • Tomislav Ilicic
  • Sandrine Imbeaud
  • Marcin Imielinsk
  • Natalie Jaeger
  • David T. W. Jones
  • David Jones
  • Stian Knappskog
  • Marcel Kool
  • Sunil R. Lakhani
  • Carlos Lopez-Otin
  • Sancha Martin
  • Nikhil C. Munshi
  • Hiromi Nakamura
  • Paul A. Northcott
  • Marina Pajic
  • Elli Papaemmanuil
  • Angelo Paradiso
  • John V. Pearson
  • Xose S. Puente
  • Keiran Raine
  • Manasa Ramakrishna
  • Andrea L. Richardson
  • Julia Richter
  • Philip Rosenstiel
  • Matthias Schlesner
  • Ton N. Schumacher
  • Paul N. Span
  • Jon W. Teague
  • Yasushi Totoki
  • Andrew N. J. Tutt
  • Rafael Valdes-Mas
  • Marit M. van Buuren
  • Laura van 't Veer
  • Anne Vincent-Salomon
  • Nicola Waddell
  • Lucy R. Yates
  • Jessica Zucman-Rossi
  • P. Andrew Futreal
  • Ultan McDermott
  • Peter Lichter
  • Matthew Meyerson
  • Sean M. Grimmond
  • Reiner Siebert
  • Elias Campo
  • Tatsuhiro Shibata
  • Stefan M. Pfister
  • Peter J. Campbell
  • Michael R. Stratton
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)415-421
Issue number7463
Publication statusPublished - 2013
Publication categoryResearch