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Promoter methylation of AREG, HOXA11, hMLH1, NDRG2, NPTX2 and Tes genes in glioblastoma

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Abstract

Epigenetic alterations alone or in combination with genetic mechanisms play a key role in brain tumorigenesis. Glioblastoma is one of the most common, lethal and poor clinical outcome primary brain tumors with extraordinarily miscellaneous epigenetic alterations profile. The aim of this study was to investigate new potential prognostic epigenetic markers such as AREG, HOXA11, hMLH1, NDRG2, NTPX2 and Tes genes promoter methylation, frequency and value for patients outcome. We examined the promoter methylation status using methylation-specific polymerase chain reaction in 100 glioblastoma tissue samples. The value for clinical outcome was calculated using Kaplan–Meier estimation with log-rank test. DNA promoter methylation was frequent event appearing more than 45 % for gene. AREG and HOXA11 methylation status was significantly associated with patient age. HOXA11 showed the tendency to be associated with patient outcome in glioblastomas. AREG gene promoter methylation showed significant correlation with poor patient outcome. AREG methylation remained significantly associated with patient survival in a Cox multivariate model including MGMT promoter methylation status. This study of new epigenetic targets has shown considerably high level of analyzed genes promoter methylation variability in glioblastoma tissue. AREG gene might be valuable marker for glioblastoma patient survival prognosis, however further analysis is needed to clarify the independence and appropriateness of the marker.

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Acknowledgments

This research was funded by a Grant (No. LIG-17/2010) from the Research Council of Lithuania. We kindly thank former Master student of VMU Ms. Dalia Gedmintaitė for her technical assistance in hMLH1 and Tes gene methylation investigation.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Neurooncology and Genetics, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, 50161, Kaunas, Lithuania

    Daina Skiriutė, Paulina Vaitkienė, Virginija Ašmonienė, Giedrius Steponaitis, Vytenis Pranas Deltuva & Arimantas Tamašauskas

  2. Department of Neurosurgery, Hospital of Lithuanian University of Health Sciences Kauno Klinikos, Eiveniu str. 2, 50161, Kaunas, Lithuania

    Vytenis Pranas Deltuva & Arimantas Tamašauskas

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  1. Daina Skiriutė
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Correspondence to Daina Skiriutė.

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Skiriutė, D., Vaitkienė, P., Ašmonienė, V. et al. Promoter methylation of AREG, HOXA11, hMLH1, NDRG2, NPTX2 and Tes genes in glioblastoma. J Neurooncol 113, 441–449 (2013). https://doi.org/10.1007/s11060-013-1133-3

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  • DOI: https://doi.org/10.1007/s11060-013-1133-3

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