Concurrent hypermethylation of DNMT1, MGMT and EGFR genes in progression of gliomas

Eva Gömöri1, József Pál, Bernadett Kovács

  • 1Department of Pathology, Faculty of Medicine, Pécs University, Hungary. eva.gomori@kk.pte.hu

Diagnostic Pathology
|January 24, 2012
PubMed
Abstract

Insights

Glioma progression involves promoter hypermethylation of MGMT and EGFR genes, which are early events. DNMT1 promoter hypermethylation is a later event in glioma development and recurrence.

Area of Science:

  • Neuro-oncology
  • Epigenetics
  • Molecular Pathology

Background:

  • Gliomas are primary brain tumors with poor prognosis.
  • High-grade gliomas often resist treatment and recur.
  • Molecular mechanisms of glioma progression are not fully understood.

Purpose of the Study:

  • To investigate the association between glioma progression and promoter methylation of DNMT1, MGMT, and EGFR genes.
  • To analyze epigenetic inactivation of these genes in paired primary and recurrent glioma samples.

Main Methods:

  • Longitudinal analysis of primary and recurrent glioma samples.
  • PCR-based restriction enzyme assay to detect promoter methylation.
  • Analysis of DNA methyltransferase 1 (DNMT1), methylguanine-DNA methyltransferase (MGMT), and epithelial growth factor receptor (EGFR) gene promoters.

Main Results:

  • MGMT and EGFR promoter hypermethylation occurred in both low- and high-grade gliomas and their transformed counterparts.
  • DNMT1 promoter hypermethylation was primarily observed in secondary glioblastomas, not low-grade gliomas.
  • Hypermethylation of MGMT and EGFR promoters was found in 10/18 and 12/18 recurrent gliomas, respectively.

Conclusions:

  • EGFR and MGMT gene inactivation through promoter hypermethylation are associated with glioma histological transformation and progression.
  • EGFR and MGMT promoter hypermethylation are early events in glioma evolution, remaining stable upon recurrence.
  • DNMT1 promoter hypermethylation appears to be a late event in glioma progression.

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