MGMT pyrosequencing-based cut-off methylation level and clinical outcome in patients with glioblastoma multiforme

Lorena Gurrieri, Elisa De Carlo, Lorenzo Gerratana, Giovanna De Maglio, Marianna Macerelli, Federica Edith Pisa, Elena Masiero, Giuseppe Aprile, Alessandro Follador, Fabio Puglisi, Gianpiero Fasola, Simona Rizzato, Stefano Pizzolitto

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: MGMT promoter methylation has been associated with improved survival in glioblastoma multiforme treated with temozolomide. However, there is no consensus on specific cut-off levels of methylation. The aims of the study were to explore the prognostic impact of MGMT methylation status and to analyze the role of specific cut-off values. Materials & methods: We analyzed 108 glioblastoma multiforme patients treated between 2008 and 2013 stratified according to three pyrosequencing-based quantitative methylation in: unmethylated (methylation <9%), intermediate (9-29%) and highly methylated (>29%). Results: The three-class stratification has a prognostic impact (median progression-free survival: 7.97, 11.6 and 15 months respectively; p = 0.004; median OS: 13.2, 15.8 and 19.5 months, respectively; p = 0.0002), especially in patients exposed to temozolomide. Conclusion: Our study confirmed that the independent prognostic role of MGMT methylation status. An average level of methylation between all investigated CpGs of 9% may help discriminating between methylated and unmethylated tumors.

Original languageEnglish
Pages (from-to)699-707
Number of pages9
JournalFuture Oncology
Volume14
Issue number8
DOIs
Publication statusPublished - Apr 1 2018

Keywords

  • CpG islands
  • cut-off
  • glioblastoma
  • IDH1
  • methylation
  • MGMT
  • pyrosequencing
  • temozolomide

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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