Blood-based DNA methylation of DNA repair genes in the non-homologous end-joining (NEHJ) pathway in patient with glioma

Int J Clin Exp Pathol. 2015 Aug 1;8(8):9463-7. eCollection 2015.

Abstract

To investigate the blood-based DNA methylation of repair genes including LIG4, XRCC4, XRCC5, XRCC6 and XRCC7 that involved in non-homologous end-joining (NEHJ) DNA repair pathway in patients with glioma. Blood samples were obtained from 114 glioma patients, 96 normal controls, and 81 glioma patients after radiotherapy and chemotherapy. Blood-based DNA methylation of the five NHEJ repair genes was assayed by methylation-specific polymerase chain reaction (MSP). The DNA methylation level of XRCC5 and XRCC7 in glioma group are significantly higher than those of normal group (P<0.001). Moreover, radiotherapy treatment significantly increased methylation level of XRCC5 and XRCC7 compared to glioma group. No significant difference for the methylation of the other three genes, LIG4, XRCC4 and XRCC6 were detected among three groups.

In conclusion: our findings indicate that DNA methylation modification plays an important role to regulate the gene expression of XRCC5 and XRCC7, from the results that the gene methylation level of the glioma group is higher than that of the normal group. Increased methylation of XRCC5 and XRCC7 in blood samples of glioma patients and patients with radiotherapy and chemotherapy suggests that blood-based methylation level of XRCC5 and XRCC7 could be a potential indicator for evaluating of the effect of radiotherapy and chemotherapy for glioma patient.

Keywords: DNA repair gene; Methylation; glioma; non-homologous end-joining.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Nuclear / genetics
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy
  • DNA End-Joining Repair*
  • DNA Helicases / genetics
  • DNA Ligase ATP
  • DNA Ligases / genetics
  • DNA Methylation*
  • DNA-Activated Protein Kinase / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Predisposition to Disease
  • Glioma / genetics*
  • Glioma / pathology
  • Glioma / radiotherapy
  • Humans
  • Ku Autoantigen
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • LIG4 protein, human
  • Nuclear Proteins
  • XRCC4 protein, human
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen
  • DNA Ligases
  • DNA Ligase ATP