MGMT promoter gene methylation in pediatric glioblastoma: analysis using MS-MLPA

Childs Nerv Syst. 2011 Nov;27(11):1877-83. doi: 10.1007/s00381-011-1525-7. Epub 2011 Jul 26.

Abstract

Purpose: Promoter methylation of the O⁶-methylguanine-DNA-methyltransferase (MGMT) gene is widely recognized as an important predictive factor in the treatment of glioblastoma (GBM) patients with temozolomide. However, data regarding the methylation status of the MGMT promoter in pediatric GBM are yet to be elucidated.

Methods: Nineteen tissue samples of pediatric GBM were evaluated for the MGMT promoter methylation status using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). Methylation status was also evaluated using methylation-specific polymerase chain reaction (MSP) for 17 of the 19 patients. The correlation between MGMT promoter methylation and clinical outcome was assessed.

Results: Three of the 19 patients (16%) showed methylation of the MGMT promoter, according to MS-MLPA, as did 1 of the 17 (6%), according to MSP. The methylation status did not seem to have a definite effect on clinical outcome.

Conclusions: Pediatric GBMs rarely have methylated MGMT promoters. With a better clinical outcome and lower methylation rate than their adult counterparts, it may be suggested that, for pediatric GBM, MGMT promoter methylation does not play a significant role as a prognostic factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Child
  • Child, Preschool
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Disease-Free Survival
  • Female
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics*
  • Glioblastoma / mortality
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Nucleic Acid Amplification Techniques*
  • Polymerase Chain Reaction / methods
  • Promoter Regions, Genetic / genetics*
  • Reproducibility of Results
  • Temozolomide
  • Tumor Suppressor Proteins / genetics*

Substances

  • Antineoplastic Agents
  • Tumor Suppressor Proteins
  • Dacarbazine
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide