Fast routine assessment of MGMT promoter methylation

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. © The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. Brief Communication

Despite recent advances in targeted diffuse glioma therapy, temozolomide still remains a therapeutic mainstay that rests on MGMT promoter methylation state as key predictor. Despite its importance in clinical decision making, MGMT testing has neither been standardized nor is it rapidly available. We, therefore, implemented an integrative diagnostic pipeline, comprising a methylation-specific PCR (MSP) complemented by a STP-27-based MGMT promoter assessment 1 within methylation array analysis. Here, we report on the diagnostic precision of this approach that provides both a rapid neuro-oncology tumor board decision tool and a safe fallback method at affordable cost.
Anonymized diagnostic and quality control data from 113 brain tumor patients from two centers (Basel, Switzerland; Naples, Italy) were analyzed. For each tumor, an integrated morphomolecular diagnosis (2016 WHO classification 2 ), methylation array data, and the MSP result were available.
Classification, tools, and integrated diagnoses: Methylation classes, copy number profiles, and MGMT promoter methylation were determined from array data as reported. 1,4 Unclear cases were verified by dimension reduction (http://www. epidip.org). Results were interpreted by board-certified neuropathologists in correlation with histology.
Methylation and coarse copy number data do not contain information traceable to individuals. According to local ethics and legal boards, such data are not classified as "personal health-related data" and are exempt from ethical permits for scientific evaluation.

Brief Communication
We present an easy-to-implement approach to fast and precise brain tumor diagnostics. Whereas nanopore sequencing-based tumor methylation profiling (nanoDx), 5 implementable in most laboratories in developed countries, can drastically minimize temporal gaps between intraoperative consultations and diagnostic methylation classification, separate MGMT testing-not yet achievable by selective nanopore sequencing 6 -remains necessary. The application of MSP for MGMT testing in conjunction with the nanoDx pipeline now enables high-precision molecular brain tumor diagnostics as well as neuro-oncological decision within 48 h.

Funding
No specific funding was obtained for this work.