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Lymphoma

Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior

Leukemia volume 20, pages 1855–1862 (2006)Cite this article

Abstract

Non-Hodgkin's lymphoma (NHL) is a group of malignancies of the immune system with variable clinical behaviors and diverse molecular features. Despite the progress made in classification of NHLs based on classical methods, molecular classifications are a work in progress. Toward this goal, we used an array-based technique called differential methylation hybridization (DMH) to study small B-cell lymphoma (SBCL) subtypes. A total of 43 genomic DMH experiments were performed. From these results, several statistical methods were used to generate a set of differentially methylated genes for further validation. Methylation of LHX2, POU3F3, HOXC10, NRP2, PRKCE, RAMP, MLLT2, NKX6.1, LRP1B and ARF4 was validated in cell lines and patient samples and demonstrated subtype-related preferential methylation patterns. For LHX2 and LRP1B, bisulfite sequencing, real-time reverse transcriptase-polymerase chain reaction and induction of gene expression following treatment with the demethylating agent, 5′-aza-2′-deoxycytidine, were confirmed. This new epigenetic information is helping to define molecular portraits of distinct subtypes of SBCL that are not recognized by current classification systems and provides valuable potential insights into the biology of these tumors.

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Acknowledgements

This study was supported by National Cancer Institute Grants CA 100055 and CA097880 (CW Caldwell) and the CRC Missouri Chair in Cancer Research, and Multiple Myeloma Research Foundation (H Shi). We thank Susan Souchek and Kathy Olson for assistance with tissue banking and Angel Surdin for expert editorial assistance. We also thank Dr Mark Ellersieck for his statistical analysis (χ2 statistics) of our data.

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Authors and Affiliations

  1. Department of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, MO, USA

    F B Rahmatpanah, S Carstens, J Guo, O Sjahputera, K H Taylor, D Duff, H Shi, S I Hooshmand, R Chitma-Matsiga & C W Caldwell

  2. Department of Health Management and Informatics, University of Missouri, Columbia, MO, USA

    J W Davis

  3. Department of Statistics, University of Missouri, Columbia, MO, USA

    J W Davis

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  1. F B Rahmatpanah
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Correspondence to C W Caldwell.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Rahmatpanah, F., Carstens, S., Guo, J. et al. Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior. Leukemia 20, 1855–1862 (2006). https://doi.org/10.1038/sj.leu.2404345

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