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Tumor Biology

, Volume 37, Issue 10, pp 13571–13579 | Cite as

Identification of MGMT promoter methylation sites correlating with gene expression and IDH1 mutation in gliomas

  • Jie Zhang
  • Jian-hui Yang
  • Jia Quan
  • Xing Kang
  • Hui-juan Wang
  • Peng-gao Dai
Original Article

Abstract

O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation was reported to be an independent prognostic and predictive factor in glioma patients who received temozolomide treatment. However, the predictive value of MGMT methylation was recently questioned by several large clinical studies. The purpose of this study is to identify MGMT gene promoter CpG sites or region whose methylation were closely correlated with its gene expression to elucidate this contradictory clinical observations. The methylation status for all CpG dinucleotides in MGMT promoter and first exon region were determined in 42 Chinese glioma patients, which were then correlated with MGMT gene expression, IDH1 mutation, and tumor grade. In whole 87 CpG dinucleotides analyzed, three distinct CpG regions covering 28 CpG dinucleotides were significantly correlated with MGMT gene expression; 10 CpG dinucleotides were significantly correlated with glioma classification (p < 0.05). Isocitrate dehydrogenase 1 (IDH1) mutation and MGMT gene hypermethylation significantly co-existed, but not for MGMT gene expression. The validation cohort of gliomas treated with standard of care and comparison of the CpGs we identified with the current CpGs used in clinical setting will be very important for gliomas individual medicine in the future.

Keywords

Glioma MGMT Methylation IDH1 Pyrosequencing Correlation analysis 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (31271353) and the Program for New Century Excellent Talents in University (NCET121048).

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2016_5153_MOESM1_ESM.docx (19 kb)
Table S1 Sequences of PCR primer and sequencing primers used for pyrosequencing reactions, annealing temperatures, and number of CpG islands covered by each primer for the respective PCR amplifications (DOCX 19 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Jie Zhang
    • 1
  • Jian-hui Yang
    • 1
  • Jia Quan
    • 1
  • Xing Kang
    • 1
  • Hui-juan Wang
    • 1
  • Peng-gao Dai
    • 1
  1. 1.National Engineering Research Center for Miniaturized Detection Systems, School of Life SciencesNorthwest UniversityXi’anChina

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