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The landscape of cancer genes and mutational processes in breast cancer

Nature volume 486, pages 400–404 (2012)Cite this article

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Abstract

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis1, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.

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Figure 1: New cancer genes established in this study and involvement of the JUN kinase signalling pathway.
Figure 2: The landscape of driver mutations in breast cancer.
Figure 3: The variation in numbers and types of mutation between individual breast cancers.
Figure 4: The mutational signature of ER+ breast cancer PD4120.
Figure 5: The relationship between age at breast cancer diagnosis and all substitutions, and for

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Accession codes

Data deposits

Genome sequence data have been deposited at the European Genome-phenome Archive under accession number EGAD00001000133. Affymetrix SNP6 data have been deposited under accession number E-MTAB-1110.

Change history

  • 20 June 2012

    An initial was added and an affiliation was corrected for author A.L.R.; a hyphen was added to author S.N.-Z.

References

  1. Stratton, M. R., Campbell, P. J. & Futreal, P. A. The cancer genome. Nature 458, 719–724 (2009)

    Article  ADS  CAS  Google Scholar 

  2. 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 

  3. Varela, I. et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 469, 539–542 (2011)

    Article  ADS  CAS  Google Scholar 

  4. Keshet, Y. & Seger, R. The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions. Methods Mol. Biol. 661, 3–38 (2010)

    Article  CAS  Google Scholar 

  5. Su, G. H. 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 

  6. Carpten, J. D. et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 448, 439–444 (2007)

    Article  ADS  CAS  Google Scholar 

  7. Park, H. S. et al. Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation. J. Biol. Chem. 277, 2573–2578 (2002)

    Article  CAS  Google Scholar 

  8. Carnero, A., Blanco-Aparicio, C., Renner, O., Link, W. & Leal, J. F. The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr. Cancer Drug Targets 8, 187–198 (2008)

    Article  CAS  Google Scholar 

  9. Wu, G. S. The functional interactions between the MAPK and p53 signaling pathways. Cancer Biol. Ther. 3, 146–151 (2004)

    Article  Google Scholar 

  10. Horlein, A. J. et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 377, 397–404 (1995)

    Article  ADS  CAS  Google Scholar 

  11. Merrell, K. W. et al. Differential recruitment of nuclear receptor coregulators in ligand-dependent transcriptional repression by estrogen receptor-alpha. Oncogene 30, 1608–1614 (2010)

    Article  Google Scholar 

  12. Jones, S. et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science 330, 228–231 (2010)

    Article  ADS  CAS  Google Scholar 

  13. Reisman, D., Glaros, S. & Thompson, E. A. The SWI/SNF complex and cancer. Oncogene 28, 1653–1668 (2009)

    Article  CAS  Google Scholar 

  14. Wiegand, K. C. et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N. Engl. J. Med. 363, 1532–1543 (2010)

    Article  CAS  Google Scholar 

  15. Spirin, K. S. et al. p27/Kip1 mutation found in breast cancer. Cancer Res. 56, 2400–2404 (1996)

    CAS  PubMed  Google Scholar 

  16. Tigli, H., Buyru, N. & Dalay, N. Molecular analysis of the p27/kip1 gene in breast cancer. Mol. Diagn. 9, 17–21 (2005)

    Article  Google Scholar 

  17. Chu, I. M., Hengst, L. & Slingerland, J. M. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nature Rev. Cancer 8, 253–267 (2008)

    Article  CAS  Google Scholar 

  18. Han, J. et al. Tbx3 improves the germ-line competency of induced pluripotent stem cells. Nature 463, 1096–1100 (2010)

    Article  ADS  CAS  Google Scholar 

  19. Howard, B. & Ashworth, A. Signalling pathways implicated in early mammary gland morphogenesis and breast cancer. PLoS Genet. 2, e112 (2006)

    Article  Google Scholar 

  20. Bamshad, M. et al. Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome. Nature Genet. 16, 311–315 (1997)

    Article  CAS  Google Scholar 

  21. Fillmore, C. M. et al. Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling. Proc. Natl Acad. Sci. USA 107, 21737–21742 (2010)

    Article  ADS  CAS  Google Scholar 

  22. Ghoussaini, M. et al. Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nature Genet. 44, 312–318 (2012)

    Article  CAS  Google Scholar 

  23. Varghese, J. S. & Easton, D. F. Genome-wide association studies in common cancers–what have we learnt? Curr. Opin. Genet. Dev. 20, 201–209 (2010)

    Article  CAS  Google Scholar 

  24. Miller, D. On the nature of susceptibility to cancer. Cancer 46, 1307–1318 (1980)

    Article  CAS  Google Scholar 

  25. Schinzel, A. C. & Hahn, W. C. Oncogenic transformation and experimental models of human cancer. Front. Biosci. 13, 71–84 (2008)

    Article  CAS  Google Scholar 

  26. Shuck, S. C., Short, E. A. & Turchi, J. J. Eukaryotic nucleotide excision repair: from understanding mechanisms to influencing biology. Cell Res. 18, 64–72 (2008)

    Article  CAS  Google Scholar 

  27. Fousteri, M. & Mullenders, L. H. Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects. Cell Res. 18, 73–84 (2008)

    Article  CAS  Google Scholar 

  28. Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26, 589–595 (2010)

    Article  Google Scholar 

  29. Ye, K., Schulz, M. H., Long, Q., Apweiler, R. & Ning, Z. Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics 25, 2865–2871 (2009)

    Article  CAS  Google Scholar 

  30. Van Loo, P. et al. Allele-specific copy number analysis of tumors. Proc. Natl Acad. Sci. USA 107, 16910–16915 (2010)

    Article  ADS  CAS  Google Scholar 

  31. Varela, I. et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 469, 539–542 (2011)

    Article  ADS  CAS  Google Scholar 

  32. Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26, 589–595 (2010)

    Article  Google Scholar 

  33. Ye, K., Schulz, M. H., Long, Q., Apweiler, R. & Ning, Z. Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics 25, 2865–2871 (2009)

    Article  CAS  Google Scholar 

  34. Van Loo, P. et al. Allele-specific copy number analysis of tumors. Proc. Natl Acad. Sci. USA 107, 16910–16915 (2010)

    Article  ADS  CAS  Google Scholar 

  35. Beroukhim, R. et al. The landscape of somatic copy-number alteration across human cancers. Nature 463, 899–905 (2010)

    Article  ADS  CAS  Google Scholar 

  36. Futreal, P. A. et al. A census of human cancer genes. Nature Rev. Cancer 4, 177–183 (2004)

    Article  CAS  Google Scholar 

  37. Greenman, C. et al. Patterns of somatic mutation in human cancer genomes. Nature 446, 153–158 (2007)

    Article  ADS  CAS  Google Scholar 

  38. Nelder, J. A. &. Wedderburn, R. Generalized linear models. J. R. Stat. Soc. A 135, 370–384 (1972)

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the Wellcome Trust (grant reference 077012/Z/05/Z) and Breakthrough Breast Cancer. P.J.C. is personally funded through a Wellcome Trust Senior Clinical Research Fellowship (grant reference WT088340MA). P.V.L. is a postdoctoral researcher at the Research Foundation - Flanders (FWO) and is a visiting scientist at the Wellcome Trust Sanger Institute, supported by a travel grant from the FWO. I.V. is supported by a fellowship from The International Human Frontier Science Program Organization. A.-L.B.-D. and A.L. are funded by the Norwegian Research Council, The Norwegian Cancer Society, The Radium Hospital Foundation and Health Region SØ. A.V.S. was supported by an ‘Interface INSERM’ grant. J.S.R.-F. is funded in part by Breakthrough Breast Cancer and is a recipient of the 2010 CRUK Future Leaders Prize. D.E. is a Principal Research Fellow of Cancer Research UK. A.T. receives financial support from the Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London, and from King’s College Hospital NHS Foundation Trust in conjunction with The Experimental Cancer Medicine Centre Initiative jointly funded by Cancer Research UK, the National Institute for Health Research, the Welsh Assembly Government, the HSC R&D Office for Northern Ireland and the Chief Scientist Office, Scotland. C.D. and C.S. received partial funding from the MEDIC foundation and the Fonds National de Recherche Scientifique. J.M. and J.F. are funded in part by a research grant from the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research. The INCa-Synergie facility received support from the Institut National du Cancer, the Fondation Synergie-Lyon-Cancer, the Canceropole Lyon Auverge Rhone Alpes and the Centre Leon Berard. A.C.V. is funded by The Ludwig Institute for Cancer Research. L.v.’t.V. and A. Broeks receive funding from the Dutch Genomics Initiative-Cancer Genomics Center. We also acknowledge support for sample collection, banking and processing from the Biological Resource Center of Institut Curie; the Breakthrough Breast Cancer Unit; P. Watson and the BCCA Tumour Tissue Repository; the Centre for Translational Genomics; A. Lane and P. T. Simpson; the Australian Biospecimens Network; the Breast Unit at Royal Brisbane and Women’s Hospital; the Dana-Farber/Harvard SPORE in breast cancer (reference CA089393); A. M. Sieuwerts; and the Singhealth Tissue Repository, Singapore. We are grateful also for the support of T. B. Tean, and acknowledge the input and guidance of P. Spellman and A. Ashworth.

Author information

Author notes

  1. Philip J. Stephens, Patrick S. Tarpey and Torill Sauer: These authors contributed equally to this work.

Authors and Affiliations

  1. Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK ,

    Philip J. Stephens, Patrick S. Tarpey, Helen Davies, Peter Van Loo, Chris Greenman, David C. Wedge, Serena Nik-Zainal, Sancha Martin, Ignacio Varela, Graham R. Bignell, Lucy R. Yates, Elli Papaemmanuil, David Beare, Adam Butler, Angela Cheverton, John Gamble, Jonathan Hinton, Mingming Jia, Alagu Jayakumar, David Jones, Calli Latimer, King Wai Lau, Stuart McLaren, David J. McBride, Andrew Menzies, Laura Mudie, Keiran Raine, Roland Rad, Michael Spencer Chapman, Jon Teague, Peter J. Campbell, P. Andrew Futreal & Michael R. Stratton

  2. Department of Human Genetics, Human Genome Laboratory, VIB and University of Leuven, Herestraat 49 Box 602, B-3000 Leuven, Belgium,

    Peter Van Loo

  3. School of Computing Sciences, University of East Anglia, Norwich NR4 7TJ, UK ,

    Chris Greenman

  4. The Genome Analysis Centre, Norwich Research Park, Norwich NR4 7UH, UK ,

    Chris Greenman

  5. Breakthrough Breast Cancer Research Unit, Research Oncology, 3rd Floor Bermondsey Wing, Guy’s Hospital Campus, Kings College London School of Medicine, London SE1 9RT, UK ,

    Lucy R. Yates & Andrew Tutt

  6. Department of Clinical Oncology, Ground floor, Lambeth Wing, Guys and St Thomas’ NHS Trust, Westminster Bridge Road, London SE1 7EH, UK,

    Lucy R. Yates

  7. Department of Oncology, Centre for Cancer Genetic Epidemiology, Strangeways Research Laboratory, Cambridge CB1 8RN, UK,

    Douglas Easton

  8. Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, Strangeways Research Laboratory, Cambridge CB1 8RN, UK,

    Douglas Easton

  9. Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, O310 Oslo, Norway

    Anita Langerød & Anne-Lise Børresen-Dale

  10. National Genotyping Center, Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Sec 2, Nankang, Taipei 115, Taiwan, China ,

    Ming Ta Michael Lee & Chen-Yang Shen

  11. Department of General Surgery, Singapore General Hospital, 169608, Singapore,

    Benita Tan Kiat Tee

  12. NCCS-VARI Translational Research Laboratory, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore ,

    Bernice Wong Huimin

  13. Department Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands,

    Annegien Broeks & Laura van ‘t Veer

  14. The University of Queensland Centre for Clinical Research, The Royal Brisbane & Women’s Hospital, Herston, Brisbane, Queensland 4029, Australia ,

    Ana Cristina Vargas & Sunil R. Lakhani

  15. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada,

    Gulisa Turashvili & Samuel A. J. R. Aparicio

  16. Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada ,

    Gulisa Turashvili & Samuel A. J. R. Aparicio

  17. Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center and Cancer Genomics Center, Postbus 2040, 3000 CA Rotterdam, Netherlands,

    John Martens & John Foekens

  18. Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA,

    Aquila Fatima, Penelope Miron & Andrea L. Richardson

  19. Department of Oncology, University of Cambridge and Cancer Research UK Cambridge Research Institute, Li Ka Shin Centre, Cambridge CB2 0RE, UK,

    Suet-Feung Chin & Carlos Caldas

  20. Universite Lyon 1, INCa-Synergie, Centre Leon Berard, 28 rue Laennec, Lyon CEDEX 08, France ,

    Gilles Thomas & Sandrine Boyault

  21. Department of Tumor Biology, Institut Curie, 26 rue d’Ulm, 75248 Paris CEDEX 05, France,

    Odette Mariani & Anne Vincent Salomon

  22. The University of Queensland School of Medicine, Herston Road, Herston, Brisbane, Queensland 4006, Australia ,

    Sunil R. Lakhani

  23. Anatomical Pathology, Pathology Queensland, The Royal Brisbane and Women’s Hospital, Herston, Brisbane, Queensland 4029, Australia ,

    Sunil R. Lakhani

  24. Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands,

    Marc van de Vijver

  25. Breast Cancer Translational Laboratory, Université Libre de Bruxelles, Jules Bordet Institute, Boulevard de Waterloo 121, 1000 Brussels, Belgium ,

    Christine Desmedt & Christos Sotiriou

  26. NIHR Cambridge Biomedical Research Centre and Cambridge Experimental Cancer Medicine Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 2QQ, UK ,

    Carlos Caldas

  27. The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, UK ,

    Jorge S. Reis-Filho

  28. Institut Curie, INSERM Unit 830, 26 rue d’Ulm, 75248 Paris CEDEX 05, France ,

    Anne Vincent Salomon

  29. K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, O318 Oslo, Norway

    Anne-Lise Børresen-Dale

  30. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, Massachusetts 02115, USA,

    Andrea L. Richardson

  31. Department of Haematology, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK,

    Peter J. Campbell

  32. Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 2XY, UK,

    Peter J. Campbell

  33. Department of Breast and Endocrine Surgery, Oslo University Hospital, O424 Oslo, Norway.,

    Rolf Karesen & Ellen Schlichting

  34. Medical Faculty, University of Oslo, O424 Oslo, Norway.,

    Rolf Karesen, Bjorn Naume & Torill Sauer

  35. Department of Oncology, Oslo University Hospital, O424 Oslo, Norway.,

    Bjorn Naume & Lars Ottestad

  36. Department of Pathology, Oslo University Hospital, O424 Oslo, Norway.,

    Torill Sauer

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  1. Philip J. Stephens
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  2. Patrick S. Tarpey
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Consortia

The Oslo Breast Cancer Consortium (OSBREAC)

  • Rolf Karesen
  • , Ellen Schlichting
  • , Bjorn Naume
  • , Torill Sauer
  •  & Lars Ottestad

Contributions

P.J.S., P.S.T. and H.D. performed analysis of the sequence data, aided by S.N.Z., I.V., G.R.B., L.R.Y., E.P., D.J.M., M.S.-C. and R.R. P.V.L. performed analysis of the SNP6 data. C.G., D.C.W., K.W.L. and D.E. performed the statistical investigations. S. Martin coordinated sample acquisition and pathology review. S. McLaren coordinated sample processing. D.B., A. Butler, J.G., J.H., M.J., A.J., D.J., A.M., K.R. and J.T. performed informatics investigations. A.C., C.L. and L.M performed technical investigations. A.L., OSBREAC, M.T.M.L., C.-Y.S., B.T.K.T., B.W.H., A. Broeks, A.C.V., G. Turashvili, J.M., A.F., P.M., S.-F.C., G. Thomas, S.B., O.M., S.R.L., M.v.d.V., L.v.’t.V., J.F., C.D., C.S., A.T., C.C., J.S.R.-F., S.A.J.R.A., A.V.S., A.-L.B.-D. and A.R. contributed samples, clinical data and scientific advice. P.J.C. and P.A.F. directed the research and contributed to the manuscript. M.R.S. directed the research and wrote the manuscript.

Corresponding author

Correspondence to Michael R. Stratton.

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Competing interests

The authors declare no competing financial interests.

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Stephens, P., Tarpey, P., Davies, H. et al. The landscape of cancer genes and mutational processes in breast cancer. Nature 486, 400–404 (2012). https://doi.org/10.1038/nature11017

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