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Lymphoma

Array-based DNA methylation profiling in follicular lymphoma

Leukemia volume 23, pages 1858–1866 (2009)Cite this article

Abstract

Quantitative methylation profiling was performed using the Illumina GoldenGate Assay in untreated follicular lymphoma (FL) (164), paired pre- and post-transformation FL (20), benign haematopoietic (24) samples and purified B and T cells from two FL cases. Methylation values allowed separation of untreated FL samples from controls with one exception, based primarily on tumour-specific gains of methylation typically occurring within CpG islands. Genes that are targets for epigenetic repression in stem cells by Polycomb Repressor Complex 2 were significantly over-represented among hypermethylated genes. Methylation profiles were conserved in sequential FL and t-FL biopsies, suggesting that widespread methylation represents an early event in lymphomagenesis and may not contribute substantially to transformation. A significant (P<0.05) correlation between FL methylation values and reduced gene expression was shown for up to 28% of loci. Methylation changes occurred predominantly in B cells with variability in the amount of non-malignant tissue between samples preventing conclusive correlation with survival. This represents an important caveat in attributing prognostic relevance to methylation and future studies in cancer will optimally require purified tumour populations to address the impact of methylation on clinical outcome.

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Acknowledgements

We are grateful for the assistance of Sameena Iqbal, Andrew Davies (Institute of Cancer, London) and Susan Oliver (Oregon Health and Sciences University), for the critical review of manuscript by Emanuela Carlotti and Carolyn Owen (Institute of Cancer, London) and for helpful discussion with Attilla Lorincz (Wolfson Institute, London), Gerd Pfeifer (City of Hope, California) and Allen Yang (University of Southern California). We also thank Christy Waterfall and Mark Gibbs at Illumina UK and Illumina Technical Support staff for their assistance. CO is a Barts–Cambridge Molecular Pathology Clinical Research Fellow funded by grant support from Cancer Research UK (MONG1E9R). DO and RL are in receipt of Medical Research Council Clinical Research Fellowships. This work was also supported by funding from Cancer Research UK (programme grant to Centre for Medical Oncology), the Cancer Research Committee of Barts and the London NHS Trust (ONAG1G5R) and by a National Institute of Health Strategic Partnering for Evaluation of Cancer Signatures Program (SPECS) grant (5 U01 CA114778).

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Authors and Affiliations

  1. Centre for Medical Oncology, Barts and the London School of Medicine and Dentistry, Institute of Cancer, London, UK

    C O'Riain, D M O'Shea, Y Yang, R Le Dieu, J G Gribben, K Summers, T A Lister & J Fitzgibbon

  2. Genome Centre, Queen Mary School of Medicine and Dentistry, London, UK

    J Yeboah-Afari, L Bhaw-Rosun, C Fleischmann & C A Mein

  3. Cancer Genetics and Epigenetics, Institute for Cancer Research, London, UK

    T Crook & P Smith

  4. Bioinformatics and Biostatistics, Cancer Research UK, Lincoln's Inn Fields, London, UK

    G Kelly

  5. Institute of Pathology, University of Würzburg, Würzburg, Germany

    A Rosenwald & G Ott

  6. Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany

    G Ott

  7. Department of Pathology, Hospital Clinic, University of Barcelona, Barcelona, Spain

    E Campo

  8. Department of Pathology, University of Arizona Cancer Centre, Tucson, A, Z, USA

    L M Rimsza

  9. Department of Immunology, Institute for Cancer Research, Rikshospitalet University Hospital, Oslo, Norway

    E B Smeland

  10. Faculty Division, Centre for Cancer Biomedicine, Norwegian Radium Hospital, University of Oslo, Oslo, Norway

    E B Smeland

  11. Department of Pathology, University of Nebraska Medical Centre, Omaha, NE, USA

    W C Chan

  12. Department of Pathology, British Columbia Cancer Centre, Vancouver, British Columbia, Canada

    N Johnson & R D Gascoyne

  13. Department of Pathology, Oregon Health and Science University, Portland, O, R, USA

    S Reimer & R M Braziel

  14. Metabolism Branch, National Cancer Institute, Bethesda, M, D, USA

    G W Wright & L M Staudt

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  1. C O'Riain
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Correspondence to C O'Riain.

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O'Riain, C., O'Shea, D., Yang, Y. et al. Array-based DNA methylation profiling in follicular lymphoma. Leukemia 23, 1858–1866 (2009). https://doi.org/10.1038/leu.2009.114

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