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Abstract

Spontaneously occurring mutations accumulate in somatic cells throughout a person’s lifetime. The majority of these mutations do not have a noticeable effect, but some can alter key cellular functions. Early somatic mutations can cause developmental disorders, whereas the progressive accumulation of mutations throughout life can lead to cancer and contribute to aging. Genome sequencing has revolutionized our understanding of somatic mutation in cancer, providing a detailed view of the mutational processes and genes that drive cancer. Yet, fundamental gaps remain in our knowledge of how normal cells evolve into cancer cells. We briefly summarize a number of the lessons learned over 5 years of cancer genome sequencing and discuss their implications for our understanding of cancer progression and aging.

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Science
Volume 349 | Issue 6255
25 September 2015

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Published in print: 25 September 2015

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Acknowledgments

We thank L. B. Alexandrov (Los Alamos National Laboratory, USA) for sharing data before publication (Fig. 1A) and the TCGA team for their invaluable public resource. Figures 1 and 2 are largely based on data generated by TCGA (http://cancergenome.nih.gov/). P.J.C. is a Wellcome Trust Senior Clinical Fellow, and I.M. is a fellow of Queens’ College, Cambridge. P.J.C. holds equity in and is a paid consultant for 14M Genomics Ltd.

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Iñigo Martincorena
Wellcome Trust Sanger Institute, Hinxton CB10 1SA, Cambridgeshire, UK.
Peter J. Campbell* [email protected]
Wellcome Trust Sanger Institute, Hinxton CB10 1SA, Cambridgeshire, UK.
Department of Haematology, University of Cambridge, Cambridge, UK.

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*
Corresponding author. E-mail: [email protected]

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