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High-frequency promoter hypermethylation of the deleted in liver cancer-1 gene in multiple myeloma
  1. Y-F Song1,
  2. R Xu2,
  3. X-H Zhang3,
  4. B-B Chen1,
  5. Q Chen1,
  6. Y-M Chen1,
  7. Y Xie1
  1. 1Department of Hematology, Hua Shan Hospital, Fu Dan University, Shanghai, China
  2. 2Center of Clinical Laboratory of Shanghai, Shanghai
  3. 3Division of Internal Medicine, 3rd Peoples Hospital of Luohe, Luohe, China
  1. Correspondence to:
    Y-F Song
    Department of Hematology, Hua Shan Hospital, Fu Dan University, 12 Wu Lu Mu Qi Zhong Road, Shanghai 200040, China; songyf03{at}yahoo.com

Abstract

Background: Deleted in liver cancer-1 (DLC-1) is a tumour suppressor gene that is inactive in liver carcinogenesis. It encodes a ρ-guanosine triphosphatase-activating protein (ρ-GAP) and maps to one of the deleted regions (8p21.3–22). Little is known, however, about the methylation status of the DLC-1 promoter in myeloma cells.

Aim: To identify whether methylation of DLC-1 was associated in pathogenesis of multiple myeloma.

Methods: Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect DLC-1 transcripts in RPMI 8226, U266, OPM-2 and XG-2 cell lines. The methylation status was determined by methylation-specific PCR followed by bisulphite DNA sequencing in these four cell lines and in the bone marrow of 14 patients with multiple myeloma and 4 normal patients. DLC-1 mRNA expression in cells with or without treatment with 5-aza-deoxycytidine (5-aza-CdR) or trichostatin A (TSA) was investigated by real-time RT-PCR.

Results: RPMI 8226 and U266 showed complete methylation and XG-2 showed partial methylation. DLC-1 was expressed only in OPM-2 cell lines that showed no methylation. DLC-1 methylation was shown in 11 of 14 (78%) patients with multiple myeloma and none of the normal controls. The exposure of cell lines to 5-aza-CdR or TSA resulted in the up regulation of DLC-1 gene expression.

Conclusions:DLC-1 methylation is often present in multiple myeloma and has a key role in DLC-1 silencing.

  • 5-aza-CdR, 5-aza-deoxycytidine
  • CpG, cytosine-deoxyribose phosphates followed immediately by a guanine-deoxyribose phosphate
  • DLC-1, deleted in liver cancer-1 gene
  • GAPDH, glyceraldehyde-3-phosphate dehydrogenase
  • GTPase, guanosine triphosphatase
  • HCC, hepatocellular carcinoma
  • HDAC, histone deacetylase inhibitor
  • MSP, methylation-specific polymerase chain reaction
  • ρ-GAP, ρ-guanosine triphosphatase-activating protein
  • RT-PCR, reverse transcription-polymerase chain reaction
  • Tm, melting temperature
  • TSA, trichostatin A

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Footnotes

  • Published Online First 17 February 2006

  • Competing interests: None declared.

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