ArticleMolecular cancer therapeutics2014
The role of gene body cytosine modifications in MGMT expression and sensitivity to temozolomide.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- Association Between Temozolomide Resistance and Long Non-Coding RNA Expression Profiles in Glioblastoma Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review).Molecular and clinical oncology · 2024Review
- Profound DNA methylomic differences between single- and multi-fraction alpha irradiations of lung fibroblasts.Clinical epigenetics · 2023Article
- Evaluation of Temozolomide and Fingolimod Treatments in Glioblastoma Preclinical Models.Cancers · 2023Article
- Changes in calpain-2 expression during glioblastoma progression predisposes tumor cells to temozolomide resistance by minimizing DNA damage and p53-dependent apoptosis.Cancer cell international · 2023Article
- Temozolomide-induced guanine mutations create exploitable vulnerabilities of guanine-rich DNA and RNA regions in drug-resistant gliomas.Science advances · 2022Article
- Modified Adenosines Sensitize Glioblastoma Cells to Temozolomide by Affecting DNA Methyltransferases.Frontiers in pharmacology · 2022Article
- Expression of 5-methylcytosine regulators is highly associated with the clinical phenotypes of prostate cancer and DNMTs expression predicts biochemical recurrence.Cancer medicine · 2021Article
- Article
- Genomic Space ofInternational journal of molecular sciences · 2021Article
- Genetic and environmental determinants of OClinical epigenetics · 2021Article
- DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association.Communications biology · 2021Article
- A novel Cas9-targeted long-read assay for simultaneous detection of IDH1/2 mutations and clinically relevant MGMT methylation in fresh biopsies of diffuse glioma.Acta neuropathologica communications · 2020Article
- Epigenetic preconditioning with decitabine sensitizes glioblastoma to temozolomide via induction of MLH1.Journal of neuro-oncology · 2020Article
- MGMT Status as a Clinical Biomarker in Glioblastoma.Trends in cancer · 2020Review
- Temozolomide in Combination With NF-κB Inhibitor Significantly Disrupts the Glioblastoma Multiforme Spheroid Formation.IEEE open journal of engineering in medicine and biology · 2020Article
- Epigenetic Reprogramming for TargetingCancers · 2019Review
- The Chk1 inhibitor SAR-020106 sensitizes human glioblastoma cells to irradiation, to temozolomide, and to decitabine treatment.Journal of experimental & clinical cancer research : CR · 2019Article
- Dehydroepiandrosterone Induces Temozolomide Resistance Through Modulating Phosphorylation and Acetylation of Sp1 in Glioblastoma.Molecular neurobiology · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is known to play a role in sensitivity to temozolomide. Promoter hypermethylation of MGMT is commonly used to predict low expression levels of MGMT in gliomas, despite observed discordance between promoter methylation and protein levels. Here, we investigated the functional role of gene body cytosine modification in regulating levels of MGMT gene expression and sensitivity to temozolomide. In 91 human glioblastoma samples, we observed significant variation in MGMT expression levels in patients with an unmethylated promoter, with higher levels of gene body cytosine modification correlating with higher gene expression levels. Furthermore, inducing hypomethylation across the MGMT gene body with decitabine corresponded with decreased levels of MGMT gene expression in lymphoblastoid and glioblastoma cell lines, indicating an important functional role for gene body cytosine modifications in maintaining gene expression. We reasoned that the decrease in MGMT expression induced by decitabine may render resistant glioblastoma cell lines more sensitive to temozolomide. Consistent with this reasoning, we found that the MGMT-expressing glioblastoma cell lines exhibiting an unmethylated MGMT promoter that were pretreated with decitabine became significantly more sensitive to temozolomide. Overall, our results suggest a functional role for gene body cytosine modification in regulating gene expression of MGMT and indicate that pretreating patients whose tumors have an unmethylated MGMT promoter with decitabine before temozolomide treatment may increase their response to therapy.
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