Cellular and Molecular Neurobiology

, Volume 32, Issue 2, pp 237–244 | Cite as

The Promoter Hypermethylation Status of GATA6, MGMT, and FHIT in Glioblastoma

  • Gulsah Cecener
  • Berrin Tunca
  • Unal Egeli
  • Ahmet Bekar
  • Gulcin Tezcan
  • Elif Erturk
  • Nuran Bayram
  • Sahsine Tolunay
Original Research

Abstract

Glioblastoma (GBM) is an aggressive and lethal cancer, accounting for the majority of primary brain tumors in adults. GBMs are characterized by large and small alterations in genes that control cell growth, apoptosis, angiogenesis, and invasion. Epigenetic alterations also affect the expression of cancer genes, either alone or in combination with genetic mechanisms. The current evidence suggests that hypermethylation of promoter CpG islands is a common epigenetic event in a variety of human cancers. A subset of GBMs is also characterized by a locus-specific and genome-wide decrease in DNA methylation. Epigenetic alterations are important in the molecular pathology of GBM. However, there are very limited data about these epigenetic alterations in GBM. Alterations in promoter methylations are important to understand because histone deacetylases are targets for drugs that are in clinical trial for GBMs. The aim of the current study was to investigate whether the promoter hypermethylation of putative tumor suppressor genes was involved in GBM. We examined the methylation status at the promoter regions of GATA6, MGMT, and FHIT using the methylation-specific polymerase chain reaction in 61 primary GBMs. Our results reveal that there is no promoter hypermethylation of FHIT in the examined GBM tissue specimens. In contrast, the promoter hypermethylation of GATA6 and MGMT was detected in 42.8 and 11.11% of GBMs, respectively. The frequency of MGMT promoter hypermethylation was low in the group of patients we evaluated. In conclusion, our study demonstrates that promoter hypermethylation of MGMT is a common event in GBMs, whereas GATA6 is epigenetically affected in GBMs. Furthermore, inactivation of FHIT by epigenetic mechanisms in GBM may not be associated with brain tumorigenesis.

Keywords

Glioblastoma GATA6 MGMT FHIT Hypermethylation 

Abbreviations

GBM

Glioblastoma

MGMT

O6-methylguanine-DNA methyltransferase

FHIT

Fragile histidine triad

IHC

Immunohistochemistry

MSP

Methylation-specific polymerase chain reaction

WHO

World Health Organization

LOH

Loss of heterozygosity

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Gulsah Cecener
    • 1
  • Berrin Tunca
    • 1
  • Unal Egeli
    • 1
  • Ahmet Bekar
    • 2
  • Gulcin Tezcan
    • 1
  • Elif Erturk
    • 1
  • Nuran Bayram
    • 4
  • Sahsine Tolunay
    • 3
  1. 1.Department of Medical Biology, School of MedicineUludag UniversityBursaTurkey
  2. 2.Department of Neurosurgery, School of MedicineUludag UniversityBursaTurkey
  3. 3.Department of Pathology, School of MedicineUludag UniversityBursaTurkey
  4. 4.Department of Econometrics, Faculty of Economics and Administrative SciencesUludag UniversityBursaTurkey

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