Frequent hypermethylation of DBC1 in malignant lymphoproliferative neoplasms.
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.
Grønbaek
Kirsten
K
Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark. kirsten.groenbaek@rh.regionh.dk
Ralfkiaer
Ulrik
U
Dahl
Christina
C
Hother
Christoffer
C
Burns
Jorge S
JS
Kassem
Moustapha
M
Worm
Jesper
J
Ralfkiaer
Elisabeth M
EM
Knudsen
Lene M
LM
Hokland
Peter
P
Guldberg
Per
P
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D018797:Cell Cycle Proteins; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C112308:BRINP1 protein, human; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins