1. ¹Centre for Medical Oncology, Barts and the London School of Medicine and Dentistry, Institute of Cancer, London, UK
2. ²Genome Centre, Queen Mary School of Medicine and Dentistry, London, UK
3. ³Cancer Genetics and Epigenetics, Institute for Cancer Research, London, UK
4. ⁴Bioinformatics and Biostatistics, Cancer Research UK, Lincoln's Inn Fields, London, UK
5. ⁵Institute of Pathology, University of Würzburg, Würzburg, Germany
6. ⁶Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany
7. ⁷Department of Pathology, Hospital Clinic, University of Barcelona, Barcelona, Spain
8. ⁸Department of Pathology, University of Arizona Cancer Centre, Tucson, AZ, USA
9. ⁹Department of Immunology, Institute for Cancer Research, Rikshospitalet University Hospital, Oslo, Norway
10. ¹⁰Faculty Division, Centre for Cancer Biomedicine, Norwegian Radium Hospital, University of Oslo, Oslo, Norway
11. ¹¹Department of Pathology, University of Nebraska Medical Centre, Omaha, NE, USA
12. ¹²Department of Pathology, British Columbia Cancer Centre, Vancouver, British Columbia, Canada
13. ¹³Department of Pathology, Oregon Health and Science University, Portland, OR, USA
14. ¹⁴Metabolism Branch, National Cancer Institute, Bethesda, MD, USA

Correspondence: Dr C O'Riain, Centre for Medical Oncology, Barts and the London School of Medicine and Dentistry, Institute of Cancer, 3rd Floor John Vane Science Building, Charterhouse Square, London EC1M 6BQ, UK. E-mail: c.l.oriain@qmul.ac.uk

Received 24 October 2008; Revised 2 April 2009; Accepted 17 April 2009; Published online 9 July 2009.

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.