Abstract
Using a candidate gene approach, we analyzed the methylation status of the promoter-associated CpG islands of 11 well-characterized tumor suppressor genes by methylation-specific polymerase chain reaction in five multiple myeloma (MM) cell lines and 56 patients with malignant plasma cell disorders. The frequency of aberrant methylation among the patient samples was 46.4% for SOCS-1, 35.7% for p16, 21.4% for E-cadherin, 12.5% for DAP kinase and p73, 1.8% for p15, MGMT as well as RARβ, and 0% for TIMP-3, RASSF1A and hMLH1. We found at least one hypermethylated gene in 80.4% of the primary patient samples, while 33.9% harbored two or more hypermethylated genes. For the first time, we show that p73 may be hypermethylated in MM and thus be involved in the pathogenesis of plasma cell disorders. Hypermethylation of p16 at diagnosis was associated with a poorer prognosis. In patients with plasma cell leukemia, we found frequent simultaneous hypermethylation of p16, E-cadherin and DAP kinase. We conclude that aberrant methylation of tumor suppressor genes is a common event in malignant plasma cell disorders and that there is a correlation between methylation patterns and clinical characteristics in MM patients.
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Acknowledgements
We thank Sandra Mellen and Ingeborg Wiegand for expert technical assistance and Albert Esser for help with the statistical analysis. This work was supported by a grant from the Rheinisch-Westfaelische Technische Hochschule Aachen (START program) and the Samuel Waxman Cancer Research Foundation. JGH is a paid consultant to and receives research support from OncoMethylome Sciences. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.
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Galm, O., Wilop, S., Reichelt, J. et al. DNA methylation changes in multiple myeloma. Leukemia 18, 1687–1692 (2004). https://doi.org/10.1038/sj.leu.2403434
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DOI: https://doi.org/10.1038/sj.leu.2403434
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