Frequent hypermethylation of DBC1 in malignant lymphoproliferative neoplasms View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-02-08

AUTHORS

Kirsten Grønbæk, Ulrik Ralfkiaer, Christina Dahl, Christoffer Hother, Jorge S Burns, Moustapha Kassem, Jesper Worm, Elisabeth M Ralfkiaer, Lene M Knudsen, Peter Hokland, Per Guldberg

ABSTRACT

Allelic loss at chromosome 9q31–34 is a frequent event in many lymphoproliferative malignancies. Here, we examined DBC1 at 9q33.1 as a potential target in lymphomagenesis. DBC1 is a putative tumor suppressor that has been shown to be involved in the regulation of cell growth and programmed cell death. The methylation status of the DBC1 promoter CpG island was examined by methylation-specific PCR, bisulfite sequencing, and methylation-specific melting curve analysis. DBC1 was hypermethylated in 5 of 5 B-cell-derived lymphoma cell lines, 41 of 42 diffuse large B-cell lymphomas, 24 of 24 follicular lymphomas, 5 of 5 mantle cell lymphomas, 4 of 4 small lymphocytic lymphomas, 1 of 2 lymphoplasmacytoid lymphomas, and in 12 of 12 acute lymphoblastic leukemias, but was unmethylated in 1 case of splenic marginal zone lymphoma, in 12 of 12 multiple myelomas, in 24 of 24 reactive lymph nodes, and in 12 of 12 samples of blood lymphocytes from random donors. DBC1 hypermethylation was associated with transcriptional silencing in lymphoma cell lines, and reexpression of this gene could be induced by treatment with the demethylating agent, 5-aza-2′-deoxycytidine. Our data suggest that hypermethylation of the DBC1 promoter region is a frequent event during the development of lymphoproliferative malignancies, and that DBC1 hypermethylation may serve as a marker for these cancers. More... »

PAGES

632-638

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/modpathol.2008.27

DOI

http://dx.doi.org/10.1038/modpathol.2008.27

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18264085


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73 islands
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92 methylation status
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