Patterns of somatic mutation in human cancer genomes (original) (raw)

References

1. Futreal, P. A. et al. A census of human cancer genes. Nature Rev. Cancer 4, 177–183 (2004)
   Article CAS Google Scholar
2. Futreal, P. A. et al. Cancer and genomics. Nature 409, 850–852 (2001)
   Article ADS CAS Google Scholar
3. Sawyers, C. Targeted cancer therapy. Nature 432, 294–297 (2004)
   Article ADS CAS Google Scholar
4. Manning, G., Whyte, D. B., Martinez, R., Hunter, T. & Sudarsanam, S. The protein kinase complement of the human genome. Science 298, 1912–1934 (2002)
   Article ADS CAS Google Scholar
5. Stephens, P. et al. A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer. Nature Genet. 37, 590–592 (2005)
   Article CAS Google Scholar
6. Davies, H. et al. Somatic mutations of the protein kinase gene family in human lung cancer. Cancer Res. 65, 7591–7595 (2005)
   Article CAS Google Scholar
7. Hunter, C. et al. A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res. 66, 3987–3991 (2006)
   Article CAS Google Scholar
8. Bignell, G. et al. Sequence analysis of the protein kinase gene family in human testicular germ-cell tumours of adolescents and adults. Genes Chromosom. Cancer 45, 42–46 (2006)
   Article CAS Google Scholar
9. Bardelli, A. et al. Mutational analysis of the tyrosine kinome in colorectal cancers. Science 300, 949 (2003)
   Article CAS Google Scholar
10. Wang, T.-L. et al. Prevalence of somatic alterations in the colorectal cancer cell genome. Proc. Natl Acad. Sci. USA 99, 3076–3080 (2002)
    Article ADS CAS Google Scholar
11. Lonardi, S., Tosoni, A. & Brandes, A. A. Adjuvant chemotherapy in the treatment of high grade gliomas. Cancer Treat. Rev. 31, 79–89 (2005)
    Article CAS Google Scholar
12. Karran, P., Offman, J. & Bignami, M. Human mismatch repair, drug-induced DNA damage, and secondary cancer. Biochimie 85, 1149–1160 (2003)
    Article CAS Google Scholar
13. Greenman, C., Wooster, R., Futreal, P. A., Stratton, M. R. & Easton, D. F. Statistical analysis of pathogenicity of somatic mutations in cancer. Genetics 173, 2187–2198 (2006)
    Article CAS Google Scholar
14. Yang, Z., Ro, S. & Rannala, B. Likelihood models of somatic mutation and codon substitution in cancer genes. Genetics 165, 695–705 (2003)
    CAS PubMed PubMed Central Google Scholar
15. Goldman, N. & Yang, Z. A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol. Biol. Evol. 11, 725–736 (1994)
    CAS PubMed Google Scholar
16. Sanchez-Cespedes, M. et al. Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res. 62, 3659–3662 (2002)
    CAS PubMed Google Scholar
17. Davies, H. et al. Mutations of the BRAF gene in human cancer. Nature 417, 949–954 (2002)
    ADS CAS Google Scholar
18. Granzier, H. L. & Labeit, S. Titin and its associated proteins: the third myofilament system of the sarcomere. Adv. Protein Chem. 71, 89–119 (2005)
    Article CAS Google Scholar
19. Machado, C. & Andrew, D. J. D-Titin: a giant protein with dual roles in chromosomes and muscles. J. Cell Biol. 151, 639–652 (2000)
    Article CAS Google Scholar
20. Machado, C., Sunkel, C. E. & Andrew, D. J. Human autoantibodies reveal Titin as a chromosomal protein. J. Cell Biol. 141, 321–333 (1998)
    Article CAS Google Scholar
21. Zastrow, M. S., Flaherty, D. B., Benian, G. M. & Wilson, K. L. Nuclear Titin interacts with A- and B-type lamins in vitro and in vivo. J. Cell Sci. 119, 239–249 (2006)
    Article CAS Google Scholar
22. Shiloh, Y. ATM and related protein kinases: safeguarding genome integrity. Nature Rev. Cancer 3, 155–168 (2003)
    Article CAS Google Scholar
23. Renwick, A. et al. ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nature Genet. 38, 873–875 (2006)
    Article CAS Google Scholar
24. Markowitz, S. et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 268, 1336–1338 (1995)
    Article ADS CAS Google Scholar
25. Howe, J. R. et al. Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nature Genet. 28, 184–187 (2001)
    Article CAS Google Scholar
26. Wan, P. T. C. et al. Mechanism of activation of the RAF–ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116, 855–867 (2004)
    Article CAS Google Scholar
27. Irusta, P. M. et al. Definition of an inhibitory juxtamembrane WW-like domain in the platelet-derived growth factor beta receptor. J. Biol. Chem. 277, 38627–38634 (2002)
    Article CAS Google Scholar
28. Teng, D. et al. Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor. Cancer Res. 57, 4177–4182 (1997)
    CAS PubMed Google Scholar
29. Su, G. et al. Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene. Cancer Res. 58, 2339–2342 (1998)
    CAS PubMed Google Scholar
30. Parsons, D. W. et al. Colorectal cancer Mutations in a signalling pathway. Nature 436, 792 (2005)
    Article ADS CAS Google Scholar
31. Bogoyevitch, M. A., Boehm, I., Oakley, A., Ketterman, A. J. & Barr, R. K. Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential. Biochim. Biophys. Acta 1697, 89–101 (2004)
    Article CAS Google Scholar
32. Kyriakis, J. M. & Avruch, J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol. Rev. 81, 807–869 (2001)
    Article CAS Google Scholar
33. Joshi-Tope, G. et al. Reactome: a knowledgebase of biological pathways. Nucleic Acids Res. 33, D428–D432 (2005)
    Article CAS Google Scholar
34. Mi, H. et al. The PANTHER database of protein families, subfamilies, functions and pathways. Nucleic Acids Res. 33, D284–D288 (2005)
    Article CAS Google Scholar
35. Kushida, T., Takagi, T. & Fukuda, K. Event ontology: a pathway-centric ontology for biological processes. Pac. Symp. Biocomput. 11, 152–163 (2006)
    Google Scholar
36. Wilkie, A., Patey, S., Kan, S., van den Ouweland, A. & Hamel, B. FGFs, their receptors, and human limb malformations: clinical and molecular correlations. Am. J. Med. Genet. 112, 266–278 (2002)
    Article Google Scholar
37. Cappellen, D. et al. Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nature Genet. 23, 18–20 (1999)
    Article CAS Google Scholar
38. Sjoblom, T. et al. The consensus coding sequences of human breast and colorectal cancers. Science 314, 268–274 (2006)
    Article ADS Google Scholar
39. Brose, M. S. et al. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res. 62, 6997–7000 (2002)
    CAS PubMed Google Scholar

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Acknowledgements

We would like to thank J. Leary and the ABN-Oncology group (funded by the National Health and Medical Research Council of Australia), the Hauenstein Foundation and the Cooperative Human Tissue Network for providing samples for analysis, G. Wu and L. Stein for the development of the joint Reactome, Panther, INOH database, and C. Marshall and N. Rahman for comments. The studies were funded by the NIH and the Wellcome Trust.

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Authors and Affiliations

1. Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK,
   Christopher Greenman, Philip Stephens, Raffaella Smith, Gillian L. Dalgliesh, Christopher Hunter, Graham Bignell, Helen Davies, Jon Teague, Adam Butler, Claire Stevens, Sarah Edkins, Sarah O’Meara, Tim Avis, Syd Barthorpe, Gurpreet Bhamra, Gemma Buck, Bhudipa Choudhury, Jody Clements, Jennifer Cole, Ed Dicks, Simon Forbes, Kris Gray, Kelly Halliday, Rachel Harrison, Katy Hills, Jon Hinton, Andy Jenkinson, David Jones, Andy Menzies, Tatiana Mironenko, Janet Perry, Keiran Raine, Dave Richardson, Rebecca Shepherd, Alexandra Small, Calli Tofts, Jennifer Varian, Tony Webb, Sofie West, Sara Widaa, Andy Yates, Peter Campbell, Richard Wooster, P. Andrew Futreal & Michael R. Stratton
2. EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK,
   Imre Vastrik, Esther E. Schmidt & Ewan Birney
3. Molecular Pathology Unit, Neurosurgical Service and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA,
   Daniel P. Cahill & David N. Louis
4. Royal Brompton Hospital, London SW3 6NP, UK,
   Peter Goldstraw & Andrew G. Nicholson
5. Ludwig Institute for Cancer Research, 1200 Brussels, Belgium,
   Francis Brasseur
6. Laboratory of Pathology/Experimental Patho-Oncology, Erasmus MC University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Josephine Nefkens Institute, 3000 DR Rotterdam, UCL 745, B-1200, The Netherlands,
   Leendert Looijenga
7. University of Pennsylvania Cancer Centre, Philadelphia, Pennsylvania 19104-6160, USA,
   Barbara L. Weber
8. Department of Gynaecological Oncology, Westmead Hospital and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead NSW 2145, Australia,
   Yoke-Eng Chiew & Anna deFazio
9. Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK,
   Mel F. Greaves & Michael R. Stratton
10. Department of Haematology, Addenbrooke’s NHS Trust and University of Cambridge, Cambridge CB2 0QQ, UK,
    Anthony R. Green
11. Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge CB1 8RN, UK,
    Douglas F. Easton
12. Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Queensland 4029, Australia,
    Georgia Chenevix-Trench
13. Van Andel Research Institute, Grand Rapids, Michigan 49503, USA,
    Min-Han Tan, Sok Kean Khoo & Bin Tean Teh
14. Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong,
    Siu Tsan Yuen & Suet Yi Leung

Authors

1. Christopher Greenman
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2. Philip Stephens
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3. Raffaella Smith
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4. Gillian L. Dalgliesh
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5. Christopher Hunter
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6. Graham Bignell
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7. Helen Davies
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8. Jon Teague
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9. Adam Butler
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10. Claire Stevens
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11. Sarah Edkins
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12. Sarah O’Meara
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13. Imre Vastrik
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14. Esther E. Schmidt
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15. Tim Avis
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16. Syd Barthorpe
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17. Gurpreet Bhamra
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18. Gemma Buck
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19. Bhudipa Choudhury
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20. Jody Clements
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21. Jennifer Cole
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22. Ed Dicks
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23. Simon Forbes
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24. Kris Gray
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25. Kelly Halliday
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26. Rachel Harrison
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27. Katy Hills
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28. Jon Hinton
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29. Andy Jenkinson
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30. David Jones
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31. Andy Menzies
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32. Tatiana Mironenko
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33. Janet Perry
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34. Keiran Raine
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35. Dave Richardson
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36. Rebecca Shepherd
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37. Alexandra Small
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38. Calli Tofts
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39. Jennifer Varian
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40. Tony Webb
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41. Sofie West
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42. Sara Widaa
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43. Andy Yates
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44. Daniel P. Cahill
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45. David N. Louis
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46. Peter Goldstraw
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47. Andrew G. Nicholson
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48. Francis Brasseur
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49. Leendert Looijenga
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50. Barbara L. Weber
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51. Yoke-Eng Chiew
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52. Anna deFazio
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53. Mel F. Greaves
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54. Anthony R. Green
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55. Peter Campbell
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56. Ewan Birney
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57. Douglas F. Easton
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58. Georgia Chenevix-Trench
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59. Min-Han Tan
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60. Sok Kean Khoo
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61. Bin Tean Teh
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62. Siu Tsan Yuen
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63. Suet Yi Leung
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64. Richard Wooster
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65. P. Andrew Futreal
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66. Michael R. Stratton
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Corresponding authors

Correspondence toP. Andrew Futreal or Michael R. Stratton.

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Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Methods and Supplementary Tables 1-5 with Legends and Supplementary Figure 1. The Supplementary Tables show protein kinase genes in the screen (Table 1); somatic mutations indentified (Table 2); cancer samples analysed (Table 3); germline variants identified (Table 4) and kinase gene ranking by probability of carrying driver mutations (Table 5). The Supplementary Figure 1 illustrates mutation prevalence in individual cancers across cancer types (PDF 2632 kb)

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Greenman, C., Stephens, P., Smith, R. et al. Patterns of somatic mutation in human cancer genomes.Nature 446, 153–158 (2007). https://doi.org/10.1038/nature05610

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• Received: 07 September 2006
• Accepted: 18 January 2007
• Issue Date: 08 March 2007
• DOI: https://doi.org/10.1038/nature05610