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Chromosomal localization of DNA methylation in small B-cell lymphoma

Leukemia volume 22, pages 638–641 (2008)Cite this article

Accumulating evidence indicates that hypermethylation of CpG islands (CGIs) is a prevalent molecular event in human cancers, and the list of genes affected continues to grow. When a normally unmethylated CGI located within the promoter or other regulatory region of a gene becomes methylated in cancer cells, the outcome is frequently a loss of expression of adjacent genes. As a step toward a better understanding of this widespread phenomenon, our laboratory utilized a microarray containing >7K CpG loci for DNA methylation analysis to survey the genome-wide methylation present in a subgroup of non-Hodgkin's lymphomas, the small B-cell lymphomas (SBCLs)1 and acute lymphoblastic leukemia (ALL).2 These studies identified several genes and loci in which differential methylation was present among histological classes, thus showing that aberrant methylation is a nonrandom event in these malignancies.

Several models have been proposed to explain the presence of the nonrandom patterns of methylation in cancer. The first postulates that a genetic event responsible for the activation of an oncogene could trigger the initiation of tumor development through dysregulation of the DNA methylation machinery. A second postulated model suggests that some DNA sequences are readily methylatable while others are not. For example, sequences could be protected from methylation by the presence of DNA binding proteins such as transcription factors, which prevent the methylation machinery from gaining physical access to DNA. Conversely, sequences that are readily methylated may contain specific DNA binding sequence motifs that aid in the recruitment of DNA methyltransferases (DNMTs). The third model is based on nuclear architecture and postulates that certain regions of the nucleus are more or less prone to aberrant methylation based on the level of chromatin compaction at any point in time. Each of these proposed models allows for establishment of nonrandom patterns of DNA methylation, but it is likely that some combinations of these proposed mechanisms are responsible for the patterns of aberrant methylation observed in cancer.

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Acknowledgements

This work was supported by the National Cancer Institute Grants CA100055 and CA097880 (CW Caldwell).

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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

    K H Taylor, F Rahmatpanah & C W Caldwell

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

    J W Davis

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  1. K H Taylor
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  2. F Rahmatpanah
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  4. C W Caldwell
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Correspondence to C W Caldwell.

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Taylor, K., Rahmatpanah, F., Davis, J. et al. Chromosomal localization of DNA methylation in small B-cell lymphoma. Leukemia 22, 638–641 (2008). https://doi.org/10.1038/sj.leu.2404921

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