{
  "abstract": "Background\n\nMGMT promoter methylation is a well-established biomarker in glioblastoma, its relevance in melanoma brain metastases remains controversial. Recent studies indicate that methylation of MGMT enhancers contributes to MGMT regulation, whereas the role of silencer methylation has not yet been investigated.Methods\n\nDNA methylation of 52 CpG sites was analyzed in regions annotated as potential silencers located in the promoter, intronic, and upstream regions of MGMT. These regions were selected based on genomic annotations and their genomic proximity to MGMT, encompassing sites to approximately 1.5 Mb upstream, without experimental validation of direct regulatory activity. Analyses were performed in glioblastoma and melanoma brain metastases using in-house developed assays based on bisulfite conversion, PCR amplification of target regions, and pyrosequencing. By integrating previously published promoter and enhancer methylation data, a DNA methylation landscape of MGMT regulatory elements was established. Associations between CpG methylation and MGMT protein expression, overall survival, patient age, and sex were evaluated.Results\n\nThe degree of methylation strongly depended on the genomic location of the respective regulatory element. Both shared and tumor-type-specific methylation patterns were observed in glioblastoma and melanoma brain metastases. Promoter-associated CpGs and selected intronic silencer-annotated regions showed associations with MGMT protein expression. In glioblastoma, several promoter-associated CpGs were associated with overall survival, whereas sex-specific and age-related effects were absent.Conclusions\n\nDNA methylation of MGMT regulatory elements is highly CpG-specific. CpG-resolved analyses reveal a complex epigenetic landscape across the MGMT locus and highlight substantial regional heterogeneity. These findings suggest that extending methylation analyses beyond the classical promoter region provides additional insights into MGMT-associated epigenetic variation and its potentical clinical associations.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.",
    "Vienna Doctoral School in Chemistry (DoSChem), University of Vienna, 1090, Vienna, Austria.",
    "Division of Neuropathology, Department of Pathology and Molecular Pathology, Kepler University Hospital GmbH, Johannes Kepler University, Linz, Austria.",
    "Clinical Research Institute for Neurosciences, Johannes Kepler University, Linz, Austria.",
    "Department of Neurosurgery, Johannes Kepler University, Kepler University Hospital GmbH, Linz, Austria.",
    "Institute of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria. margit.cichna@univie.ac.at."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Katharina Pühringer"
    },
    {
      "affs": [
        0
      ],
      "name": "Fabian Firlinger"
    },
    {
      "affs": [
        0
      ],
      "name": "Benno Fehringer"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Serge Weis"
    },
    {
      "affs": [
        4,
        3
      ],
      "name": "Sabine Spiegl-Kreinecker"
    },
    {
      "affs": [
        5
      ],
      "name": "Margit Cichna-Markl",
      "orcid": "0000-0001-8699-674X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6pk88z9cdgq3r.bib",
  "cited_by": 0,
  "doi": "10.1186/s13148-026-02204-y",
  "fulltext_url": "https://europepmc.org/articles/PMC13721255",
  "id": "6pk88z9cdgq3r",
  "issns": [
    "1868-7083",
    "1868-7075"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958347",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W7172089638",
  "pdf_url": "https://europepmc.org/articles/PMC13721255?pdf=render",
  "pmcid": "PMC13721255",
  "pmid": "42958347",
  "published": "2026-08-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/6pk88z9cdgq3r.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:47Z",
      "native_id": "MED:42958347",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958347"
    },
    {
      "first_seen": "2026-11-03T12:21:58Z",
      "native_id": "PMC13721255",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s13148-026-02204-y"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Epigenetics and DNA Methylation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "DNA methylation of silencer-annotated regions at the MGMT locus in the context of promoter and enhancer methylation in glioblastoma and melanoma brain metastases.",
  "title_text": "DNA methylation of silencer-annotated regions at the MGMT locus in the context of promoter and enhancer methylation in glioblastoma and melanoma brain metastases.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:58Z",
  "url": "https://research.draconitic.com/paper/6pk88z9cdgq3r",
  "venue": "Clinical epigenetics",
  "versions": []
}