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Published on: December 1, 2013

Hypermethylation-mediated partial transcriptional silencing of DAP-kinase gene in bladder cancer

Ranbir Chander Sobti1, Kianoosh MalekZadeh, Mohsen Nikbakht

  • 1Department of Biotechnology, Panjab University, Chandigarh, India.

Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
|December 5, 2009
PubMed

Insights

Hypermethylation of the Death-associated protein kinase (DAP-kinase) gene promoter is common in bladder cancer, particularly in smokers over 60. This epigenetic change reduces DAP-kinase expression, increasing bladder cancer risk and potentially serving as a prognostic indicator.

Area of Science:

  • Cancer Biology
  • Epigenetics
  • Molecular Oncology

Background:

  • Death-associated protein kinase (DAP-kinase) is a serine/threonine kinase crucial for interferon-gamma-induced apoptosis.
  • Hypermethylation of gene promoters is an early and frequent event in cancer development.
  • Transitional cell carcinoma of the bladder is the focus of this study regarding DAP-kinase gene alterations.

Purpose of the Study:

  • To investigate the methylation pattern of the DAP-kinase gene in bladder cancer.
  • To assess the impact of DAP-kinase gene promoter methylation on its expression.
  • To correlate DAP-kinase methylation with clinicopathological features and bladder cancer risk.

Main Methods:

  • Analysis of DAP-kinase gene promoter methylation frequency in bladder tumors.
  • Correlation of methylation status with patient age, smoking habits, and tumor stage.
  • Quantification of DAP-kinase mRNA expression levels in relation to methylation.
  • Statistical analysis to determine the risk and odds ratios associated with methylation.

Main Results:

  • Hypermethylation of the DAP-kinase gene promoter was observed in 37.8% of bladder tumors.
  • Methylation was more frequent in superficial tumors, in patients over 60, and in smokers.
  • Carrying methylated DAP-kinase increased bladder cancer risk 6.70-fold, with elevated risk in smokers.
  • Gene promoter methylation significantly decreased DAP-kinase mRNA expression by 27.68%.

Conclusions:

  • DAP-kinase gene promoter hypermethylation is a significant event in bladder cancer development.
  • Reduced DAP-kinase expression due to methylation may contribute to malignant transformation.
  • DAP-kinase methylation serves as a potential prognostic indicator for bladder cancer progression.

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