Association of aberrant DNA methylation with clinicopathological features in breast cancer

Oncol Rep. 2012 May;27(5):1630-8. doi: 10.3892/or.2011.1576. Epub 2011 Dec 5.

Abstract

Aberrant DNA methylation is responsible for the epigenetic silencing of genes associated with tumourigenesis and progression of cancer. In this study, we assessed the methylation status of eight genes in 49 snap-frozen primary breast tumours. Epigenetic alterations of 8 genes were analysed with methylation-specific polymerase chain reaction (MS-PCR) (DCR1, DAPK1, RASSF1A and DCR2) or methylation-sensitive high-resolution melting analysis (MS-HRM) (APC, MGMT, GSTP1 and PTEN). MS-HRM performance was validated by bisulfite pyrosequencing regarding the methylation levels of MGMT. Promoter methylation was observed in APC 54.34%, 40.4% DCR1, 37.5% DAPK1, 33.3% RASSF1A, 22.44% MGMT, 16.6% GSTP1, 6% PTEN and 0% DCR2 promoters, respectively. Interestingly, 37 out of 49 cases (75.5%) displayed aberrant promoter methylation in at least one gene. An association of MGMT promoter methylation with age and tumour grade was recorded. Moreover, a correlation with advanced T-category was elicited for GSTP1, RASSF1 and DAPK1 promoter methylation. Finally, concurrent methylation of several genes showed a marginal statistical relationship with N-category. We conclude that APC, DCR1, DAPK1 and RASSF1A promoter methylation represents a common event in breast cancer tumourigenesis. Our results suggest that GSTP1, RASSF1, DAPK1 and MGMT may be implicated in the acquisition of a more aggressive phenotype in breast cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • DNA Methylation*
  • Death-Associated Protein Kinases
  • Epigenesis, Genetic
  • Female
  • GPI-Linked Proteins / genetics
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Promoter Regions, Genetic
  • Receptors, Tumor Necrosis Factor, Member 10c
  • Tumor Necrosis Factor Decoy Receptors / genetics
  • Tumor Suppressor Proteins / genetics

Substances

  • Apoptosis Regulatory Proteins
  • GPI-Linked Proteins
  • RASSF1 protein, human
  • Receptors, Tumor Necrosis Factor, Member 10c
  • TNFRSF10C protein, human
  • TNFRSF10D protein, human
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Suppressor Proteins
  • DAPK1 protein, human
  • Death-Associated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases