title: MGMT testing allows for personalised therapy in the temozolomide era.
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 O(6)-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.
authors.affiliation: Applied Radiation Therapy Trinity, Trinity College Dublin, Dublin, Ireland.|Discipline of Radiation Therapy, Trinity Centre for Health Sciences, James's street, Dublin 8, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Dullea
authors.affiliation: Applied Radiation Therapy Trinity, Trinity College Dublin, Dublin, Ireland. marignl@tcd.ie.|Discipline of Radiation Therapy, Trinity Centre for Health Sciences, James's street, Dublin 8, Ireland. marignl@tcd.ie.
authors.forename: L
authors.initials: L
authors.lastname: Marignol
mesh_terms: D000368:Aged; D019175:DNA Methylation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D020868:Gene Silencing; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000532:radiotherapy; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D057285:Precision Medicine / Q000379:methods*; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide
keywords: Glioma; MGMT; Temozolomide