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Array-based DNA methylation analysis in classical Hodgkin lymphoma reveals new insights into the mechanisms underlying silencing of B cell-specific genes

Leukemia volume 26, pages 185–188 (2012)Cite this article

Classical Hodgkin lymphoma (cHL) is an atypical germinal center derived B-cell lymphoma (gcdBCL) that has lost its B-cell identity.1 Some reports have suggested that epigenetic modifications are involved in this cHL-associated B-cell reprogramming.2, 3 Here, aiming at investigating DNA methylation patterns on a more genome-wide level, we have performed 27K BeadArray analysis4 in five cHL cell lines. Owing to the low numbers of tumor cells in primary cHL biopsies (∼1%), our microarray analyses were restricted to cHL cell lines, which represent widely used models to study this lymphoma. The results from cHL cell lines were compared with those of 20 previously analysed gcdBCL diagnosed as Burkitt lymphomas and diffuse large B-cell lymphomas5 and three normal B-cell (NBC) populations6 (for details see Supplementary Information). Results of the BeadArray analysis were exemplary validated by bisulfite pyrosequencing (Supplementary Figure S2).

After filtering sex chromosome-specific and low-quality CpGs (outlined in the Supplementary Information), a total of 24 312 autosomal CpGs corresponding to 13 088 genes entered the statistical analyses. We initially classified these CpGs according to their methylation status in NBC. We identified 16 446 CpGs unmethylated in NBC (mean β- values <0.25 and all individual β-values below 0.5), 2781 CpGs methylated in NBC (mean β-values >0.75 and all individual β-values above 0.5) and 5085 CpGs partially methylated in NBC (mean β-values between 0.25 and 0.75). As we aimed at identifying genes clearly hyper- or hypomethylated in lymphomas as compared with NBCs, this third group was not used for further analyses.

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Acknowledgements

This study has been supported by the Deutsche Krebshilfe through the project numbers 107748 to RS, 107736 and 108687 to RK, and the network project ‘Molecular Mechanisms in Malignant Lymphomas’ subproject M2 (70-3173-Tr3 to RS and JIM-S), the Ministerio de Ciencia e Innovación (SAF2009-08663 to JIM-S), the Wilhelm Sander Stiftung (2005.168.2 to RS and RK) and the Kinderkrebsinitiative Buchholz/Holm-Seppensen (pyrosequencing infrastructure to RS). JIM-S is a Ramon y Cajal researcher of the Ministerio de Ciencia e Innovación. MG is supported by a FEBS Long-Term Fellowship and Support for International Mobility of Scientists fellowships of the Polish Ministry of Science and Higher Education.

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Author notes

  1. J I Martín-Subero and R Siebert: These authors share senior authorship.

Authors and Affiliations

  1. Institute of Human Genetics, Christian-Albrechts University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    O Ammerpohl, A Haake, S Pellissery, M Giefing, J Richter, J I Martín-Subero & R Siebert

  2. Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland

    M Giefing

  3. Cancer Epigenetics and Biology Program, Bellvitge Institute for Biomedical Research, Barcelona, Spain

    B Balint

  4. Hematopathology Section, Laboratory of Pathology, Hospital Clínic, University of Barcelona, Barcelona, Spain

    M Kulis

  5. Illumina Inc., San Diego, CA, USA

    J Le & M Bibikova

  6. Department of Human and Animal Cell Cultures, DSMZ-German Collection of Microorganisms & Cell Cultures, Braunschweig, Germany

    H G Drexler

  7. Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany

    M Seifert & R Küppers

  8. Department of Pathology, Weill Cornell Medical College, New York, NY, USA

    R Shaknovic

  9. Genomics and Proteomics Core Facility, German Cancer Research Center, Heidelberg, Germany

    B Korn

  10. Department of Anatomic Pathology, Pharmacology and Microbiology, Faculty of Medicine, University of Barcelona, Barcelona, Spain

    J I Martín-Subero

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  1. O Ammerpohl
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Corresponding author

Correspondence to J I Martín-Subero.

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Competing interests

JL and MB are (or were at the time of the research) employees and stockholders of Illumina Inc. OA and JIM-S have received an honorarium for speaking in a meeting organized by Illumina.

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Supplementary Information accompanies the paper on the Leukemia website

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Ammerpohl, O., Haake, A., Pellissery, S. et al. Array-based DNA methylation analysis in classical Hodgkin lymphoma reveals new insights into the mechanisms underlying silencing of B cell-specific genes. Leukemia 26, 185–188 (2012). https://doi.org/10.1038/leu.2011.194

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