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A sensitivity analyses corroborated the performance of the original cutoff for various optimization criteria and for most data preprocessing methods. This implies some MGMT expression, potentially conferring residual repair function blunting the therapeutic effect of alkylating agents. The association between gene copy number variation, predicted MGMT methylation, and MGMT expression revealed a gene dosage effect on MGMT expression in lower grade glioma (World Health Organization grade II/III) that in contrast to glioblastoma usually carry two copies of chromosome 10 on which MGMT resides (10q26.3). Here, we investigate the impact of the context of genetic and epigenetic alterations and tumor type on the classification and report on technical aspects, such as robustness of cutoff definition and preprocessing of the data.
Our model MGMT-STP27 allows prediction of the methylation status of the MGMT promoter using data from the Illumina's Human Methylation BeadChips (HM-27K and HM-450K) that is publically available for many cancer data sets. The methylation status of the O 6-methylguanine-DNA methyltransferase ( MGMT) gene is an important predictive biomarker for benefit from alkylating agent therapy in glioblastoma.