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Glioblastoma Patients: p15 Methylation as a Prognostic Factor

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Tumors of the Central Nervous System, Volume 1

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 1))

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Abstract

Glioblastomas are the most frequent and malignant brain tumors in adults. Surgical cure is virtually impossible and despite of radiation and chemotherapy the clinical course is very poor. Epigenetic silencing of MGMT has been associated with a better response to temozolomide-chemotherapy. We previously showed that temozolomide increases the median survival time of patients with tumors harbouring deletions on 9p within the region for p15(INK4b), p16(INK4a), and 10q (MGMT). The aim of this study was to investigate the methylation status of p15, p16, 14ARF and MGMT in glioblastomas and to correlate the results with the clinical data. Only patients with KPS >70, radical tumor resection, radiation and temozolomide-chemotherapy after recurrence were included. We observed promoter methylation of MGMT in 56% (15/27) and of p15 in 37% (10/27) of the tumors, whereas methylation of p16 and p14ARF were rare. Interestingly, methylation of p15 emerged as a significant predictor of shorter overall survival (16.9 vs. 23.8 months, p = 0.025), whereas MGMT promoter methylation had no significant effect on median overall survival under this treatment regimen (22.5 vs. 22.1 months, p = 0.49). In the presence of other clinically relevant factors, p15 methylation remains the only significant predictor (p = 0.021; Cox regression). Although these results need to be confirmed in larger series and under different treatment conditions, our retrospective study shows clear evidence that p15 methylation can act as an additional prognostic factor for survival. This tumor suppressor gene, involved in cell cycle control, can act as an attractive candidate for therapeutic approaches in glioblastomas.

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Authors and Affiliations

  1. Department of Neurosurgery/Neurooncology, Saarland University, 66421, Homburg, Germany

    Steffi Urbschat, Silke Wemmert & Ralf Ketter

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  1. Steffi Urbschat
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  2. Silke Wemmert
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  3. Ralf Ketter
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Correspondence to Steffi Urbschat .

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Editors and Affiliations

  1. Dept. Biological Sciences, Kean University, 1000 Moris Avenue, Union, 07083, New Jersey, USA

    M. A. Hayat

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Urbschat, S., Wemmert, S., Ketter, R. (2011). Glioblastoma Patients: p15 Methylation as a Prognostic Factor. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 1. Tumors of the Central Nervous System, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0344-5_42

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  • DOI: https://doi.org/10.1007/978-94-007-0344-5_42

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