ArticleClinical epigenetics2022
Bisulfite profiling of the MGMT promoter and comparison with routine testing in glioblastoma diagnostics.
Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Quantitative DNA melting analysis with hybridization probes (qDMA-HP) as a novel approach to assess MGMT promoter methylation in malignant glioma.Journal of neuro-oncology · 2026Article
- A Comparison of Three Different Deep Learning-Based Models to Predict the MGMT Promoter Methylation Status in Glioblastoma Using Brain MRI.Journal of digital imaging · 2023Article
- Integration of single-cell RNA sequencing and spatial transcriptomics to reveal the glioblastoma heterogeneity.F1000Research · 2022Review
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundPromoter methylation of the DNA repair gene O
resultsTo better rationalize the variation across assays, we compared these standard techniques and assays to deep bisulfite sequencing results in a cohort of 80 malignant astrocytomas. Our deep analysis covers 49 CpG sites of the expanded MGMT promoter, including exon 1, parts of intron 1 and a region upstream of the transcription start site (TSS). We observed that deep sequencing data are in general in agreement with CpG-specific pyrosequencing, while the most widely used MSP assays published by Esteller et al. (N Engl J Med 343(19):1350-1354, 2000. https://doi.org/10.1056/NEJM200011093431901 ) and Felsberg et al. (Clin Cancer Res 15(21):6683-6693, 2009. https://doi.org/10.1158/1078-0432.CCR-08-2801 ) resulted in partially discordant results in 22 tumors (27.5%). Local deep bisulfite sequencing (LDBS) revealed that CpGs located in exon 1 are suited best to discriminate methylated from unmethylated samples. Based on LDBS data, we propose an optimized MSP primer pair with 83% and 85% concordance to pyrosequencing and LDBS data. A hitherto neglected region upstream of the TSS, with an overall higher methylation compared to exon 1 and intron 1 of MGMT, is also able to discriminate the methylation status.
conclusionOur integrated analysis allows to evaluate and redefine co-methylation domains within the MGMT promoter and to rationalize the practical impact on assays used in daily routine diagnostics.
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