Frequent hypermethylation of RASSF1A and TSLC1, and high viral load of Epstein-Barr Virus DNA in nasopharyngeal carcinoma and matched tumor-adjacent tissues

Neoplasia. 2005 Sep;7(9):809-15. doi: 10.1593/neo.05217.

Abstract

We examined the promoter hypermethylation of tumor-suppressor genes RASSF1A and TSLC1, quantitated EBV DNA load in nasopharyngeal carcinoma (NPC) tissues (T tissues), and matched tumor-adjacent tissues outside 0.5 cm (P tissues) and outside 1.0 cm (Z tissues) to evaluate the role of promoter hypermethylation of RASSF1A and TSLC1 as well as viral load in the pathogenesis of NPC. Methylation-specific polymerase chain reaction (PCR) for RASSF1A and TSLC1 and quantitative real-time PCR analysis of EBV DNA were performed on matched T, P, and Z tissues (n = 28) as well as chronic nasopharyngitis tissues (n = 8). Hypermethylated RASSF1A was frequently detected in the T (82%) and P tissues (75%), but less frequently in Z tissues (46%). he average quantities of EBV DNA (copies/microg DNA) in matched T, P, and Z tissues were 673,000, 90,000, and 7000. The differences of promoter hypermethylation of RASSF1A and EBV viral load among T, P, and Z tissues were statistically significant, with more frequent methylation and higher viral load detected when tissues examined were nearer to the NPC tissues. Our results suggest that aberrant hypermethylation of RASSF1A and high EBV load might be important events in NPC pathogenesis, and they may be useful molecular diagnostic markers for this cancer.

MeSH terms

  • Adult
  • Aged
  • Carcinoma / diagnosis
  • Carcinoma / genetics*
  • Carcinoma / virology*
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Cell Line, Tumor
  • DNA Methylation
  • DNA, Viral / analysis
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Immunoglobulins / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Nasopharyngeal Neoplasms / diagnosis
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / virology*
  • Nasopharyngitis / virology
  • Promoter Regions, Genetic
  • Tumor Suppressor Proteins / genetics*
  • Viral Load

Substances

  • CADM1 protein, human
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • DNA, Viral
  • Immunoglobulins
  • Membrane Proteins
  • RASSF1 protein, human
  • Tumor Suppressor Proteins