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DNA methylation profiling reveals a predominant immune component in breast cancers

  1. Sarah Dedeurwaerder1,†,
  2. Christine Desmedt2,†,
  3. Emilie Calonne1,
  4. Sandeep K. Singhal2,
  5. Benjamin Haibe-Kains2,3,
  6. Matthieu Defrance1,
  7. Stefan Michiels2,
  8. Michael Volkmar1,
  9. Rachel Deplus1,
  10. Judith Luciani1,
  11. Françoise Lallemand2,
  12. Denis Larsimont4,
  13. Jérôme Toussaint2,
  14. Sandy Haussy2,
  15. Françoise Rothé2,
  16. Ghizlane Rouas2,
  17. Otto Metzger2,
  18. Samira Majjaj2,
  19. Kamal Saini2,
  20. Pascale Putmans1,
  21. Gérald Hames5,
  22. Nicolas van Baren6,
  23. Pierre G. Coulie5,
  24. Martine Piccart7,
  25. Christos Sotiriou2,†,*,
  26. François Fuks1,†,*

Article first published online: 16 NOV 2011

DOI: 10.1002/emmm.201100801

Issue

EMBO Molecular Medicine

EMBO Molecular Medicine

Volume 3, Issue 12, pages 726–741, December 2011

Additional Information

How to Cite

Dedeurwaerder, S., Desmedt, C., Calonne, E., Singhal, S. K., Haibe-Kains, B., Defrance, M., Michiels, S., Volkmar, M., Deplus, R., Luciani, J., Lallemand, F., Larsimont, D., Toussaint, J., Haussy, S., Rothé, F., Rouas, G., Metzger, O., Majjaj, S., Saini, K., Putmans, P., Hames, G., van Baren, N., Coulie, P. G., Piccart, M., Sotiriou, C. and Fuks, F. (2011), DNA methylation profiling reveals a predominant immune component in breast cancers. EMBO Mol Med, 3: 726–741. doi: 10.1002/emmm.201100801

Author Information

  1. 1

    Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium

  2. 2

    Breast Cancer Translational Research Laboratory J.C. Heuson, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium

  3. 3

    Machine Learning Group, Computer Science Department, Université Libre de Bruxelles, Brussels, Belgium

  4. 4

    Pathology Department, Jules Bordet Institute, Brussels, Belgium

  5. 5

    de Duve Institute, Université Catholique de Louvain, Brussels, Belgium

  6. 6

    Ludwig Institute for Cancer Research, Brussels Branch, Belgium

  7. 7

    Medical Department, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium

  1. †

    These authors contributed equally to this work.

*Tel: +32 2 5413428; Fax: +32 2 5413339

Publication History

  1. Issue published online: 1 DEC 2011
  2. Article first published online: 16 NOV 2011
  3. Accepted manuscript online: 12 SEP 2011 03:20AM EST
  4. Manuscript Accepted: 5 SEP 2011
  5. Manuscript Revised: 1 SEP 2011
  6. Manuscript Received: 18 JUL 2011

Funded by

  • Funded Access
  • F.N.R.S.
  • Télévie
  • ‘Plan National Cancer’
  • Brussels Region ‘BruBreast’
  • ‘Interuniversity Attraction Poles’. Grant Number: IAP P6/28
  • E.U.. Grant Number: CANCERDIP FP7-200620
  • European Molecular Biology Organization Young Investigator Programme (EMBO YIP)

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Keywords:

  • breast cancer;
  • DNA methylation;
  • epigenetics;
  • epigenomics;
  • microenvironment

Abstract

Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimizing treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease are still poorly understood. By means of DNA methylation profiling of 248 breast tissues, we have highlighted the existence of previously unrecognized breast cancer groups that go beyond the currently known ‘expression subtypes’. Interestingly, we showed that DNA methylation profiling can reflect the cell type composition of the tumour microenvironment, and in particular a T lymphocyte infiltration of the tumours. Further, we highlighted a set of immune genes having high prognostic value in specific tumour categories. The immune component uncovered here by DNA methylation profiles provides a new perspective for the importance of the microenvironment in breast cancer, holding implications for better management of breast cancer patients.

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