The Next Generation of Glioma Biomarkers: MGMT Methylation, BRAF Fusions and IDH1 Mutations

Abstract

For some, glioma biomarkers have been expected to solve common diagnostic problems in routine neuropathology service caused by insufficient material, technical shortcomings or lack of experience. Further, biomarkers should predict patient outcome and direct optimal therapy for the individual patient. Unfortunately, current biomarkers still fall somewhat short of these grand expectations. While there has been some progress, it has generally been slow and in small steps. In this review, the newest set of glioma biomarkers: O(6) -methylguanine-DNA methyltransferase (MGMT) methylation, BRAF fusion and IDH1 mutation are discussed. MGMT methylation is well established as a prognostic/predictive marker for glioblastoma; however, technical questions regarding testing remain, it is not currently utilized widely in guiding patient management, and it has proven to be of no assistance in diagnostics. In contrast, BRAF fusion and IDH1 mutation analyses promise to be very helpful for classifying and grading gliomas, while their potential predictive value has yet to be established.

Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution

“…Unfortunately, studies that critically compare all assays and systematically analyze which CpG sites best reflect treatment outcome and patient survival are still lacking. 35 In line with previous reports, our results show that patients with a glioma harboring a methylated MGMT promoter generally had a longer overall survival. However, in our series in glioblastoma patients aged 450, MGMT promoter methylation no longer signified survival benefit.…”

Association between the XRCC1 Arg194Trp Polymorphism and Glioma Risk: an Updated Meta-analysis

“…At present, notwithstanding some risk factors have been found, the etiology of glioma is still poorly understood (Kishida et al, 2012, Marumoto et al, 2012. However, as we all know that genetic factors play crucial roles in the occurrence of glioma (Melin, 2011;von Deimling et al, 2011). DOI:http://dx.doi.org/10.7314/APJCP.2014.15.17.7419 Association between the XRCC1 Arg194Trp Polymorphism and Glioma Risk: an Updated Meta-analysis to make early diagnosis, predict patients outcome, or carry out individualized or personalized therapy.…”

The hypermethylation of the O6‐methylguanine‐DNA methyltransferase gene promoter in gliomas—correlation with array comparative genome hybridization results and IDH1 mutation

“…Currently, the most relevant molecular markers in diagnostics of diffuse gliomas include 1p/19q deletion, MGMT promoter hypermethylation, and IDH1 mutation (Jansen et al, 2010;Riemenschneider et al, 2010;von Deimling et al, 2011). In this study, we have assessed associations between gene copy number changes by array CGH, methylation status of MGMT gene by pyrosequencing and IDH1 mutation status by immunohistochemistry in different glioma subtypes.…”