Tumor Biology

, Volume 37, Issue 1, pp 87–96 | Cite as

MGMT testing allows for personalised therapy in the temozolomide era

Review

Abstract

Adjuvant temozolomide (TMZ)-based chemoradiation is the standard of care for most glioblastoma patients (GBMs); however, a large proportion of these patients do not respond to TMZ. Silencing of the O6-methylguanine-DNA methyltransferase (MGMT) promoter is thought to induce chemosensitivity, and testing for methylation may allow for patient stratification; however, this has yet to become routine clinical practice despite an abundance of literature on the subject. The databases PubMed, Embase, The Cochrane Library, Science Direct and Medline were searched for relevant articles published between 1999 and 2015. Articles utilising MGMT testing in glioblastomas, and treatment of glioblastomas with temozolomide were assessed. Immunohistochemistry, methylation-specific PCR (MSP), reverse transcriptase PCR, pyrosequencing and bisulphite sequencing were the main testing methods identified. Nested-MSP techniques produced poor correlation with survival, whilst bisulphite sequencing showed no evident benefit over MSP. Testing is limited by sample quality and contamination; however, efforts are made to minimise this. Strong evidence for MGMT-based personalised therapy was presented in the elderly but remains controversial in the entire GBM population. MGMT testing presents many obstacles yet to be overcome, and these warrant attention prior to the routine implementation of MGMT testing to aid decision making in GBMs. However, there is evidence to support its use, particularly in the elderly.

Keywords

Glioma Temozolomide MGMT 

Abbreviations

TMZ

Temozolomide

GBM

Glioblastoma multiforme

MGMT

O6-Methylgaunine-DNA methyltransferase

CpG

Cytosine-phosphate-guanine

OS

Overall survival

PFS

Progression-free survival

IHC

Immunohistochemistry

PCR

Polymerase chain reaction

MSP

Methylation-specific polymerase chain reaction

FFPE

Formalin-fixed paraffin-embedded

Stupp protocol

Concomitant temozolomide and radiotherapy + adjuvant temozolomide

EORTC

European Organisation for Research and Treatment of Cancer

NCIC

National Cancer Institute of Canada

RTOG

Radiation Therapy Oncology Group

KPS

Karnofsky performance status

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Applied Radiation Therapy TrinityTrinity College DublinDublinIreland
  2. 2.Discipline of Radiation TherapyTrinity Centre for Health SciencesDublin 8Ireland

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