Defining a prognostic score based on O6-methylguanine-DNA methyltransferase cut-off methylation level determined by pyrosequencing in patients with glioblastoma multiforme

Elisa De Carlo, Lorenzo Gerratana, Giovanna De Maglio, Vanessa Buoro, Francesco Cortiula, Lorena Gurrieri, Miriam Isola, Gianpiero Fasola, Fabio Puglisi, Stefano Pizzolitto, Simona Rizzato

Research output: Contribution to journalArticle

Abstract

Purpose: Epigenetic variations in the O6-methylguanine-methyltransferase gene had been widely associated with a favorable impact on survival in patients affected by glioblastoma multiforme (GBM). Aim of this study is to explore a scoring system based on the gene promoter methylation in order to predict patients’ prognosis. Methods: A series of 128 patients with GBM was retrospectively analyzed. A training set and a validations set were then generated. The methylation level of CpGi from 74 to 83 was determined by pyrosequencing. In accordance to previous literature, each island was assigned with 1 point if the corresponding methylation level was higher than 9%. The sum consisted in a score that went from 0 (all CpGi < 9%) to 10 (all CpGi ≥ 9%). A threshold capable to detect a favorable outcome (overall survival, OS > 24 months) was identified by ROC analysis. Results: Median OS and follow-up were 14 and 32.6 months respectively. Among the total population, 35% of the pts had a score of 0, while 29% had a score of 10. A score ≥ 6 was associated with a favorable prognosis also when corrected for age (> 70 vs. ≤ 70 years) and ECOG performance status (0–1 vs. 2–3). Similar results were observed also in terms of PFS. Results were consistent in the training and in the validation set. Conclusions: The present manuscript explored a novel scoring system capable to take into consideration the methylation status of each single CpGi, capable to better predict prognosis in GBM patients.

Original languageEnglish
Pages (from-to)559-568
Number of pages10
JournalJournal of Neuro-Oncology
Volume140
Issue number3
DOIs
Publication statusPublished - Dec 15 2018

Keywords

  • CpG islands
  • Glioblastoma multiforme
  • MGMT cut-off methylation level
  • Prognostic score

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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