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Updated: Jul 22, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Molecular predictors for decitabine efficacy in meningiomas - a pilot study
Dorothee C Spille1, Christian Thomas2, Andrea Wagner2
1Department of Neurosurgery, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, North Rhine-Westphalia, Germany.
Purpose:
Effective chemotherapeutical agents for the treatment of meningiomas are still lacking. Previous in-vitro analyses revealed efficacy of decitabine (DCT), a DNA methyltransferase (DNMT) inhibitor established in the treatment of leukemia, in a yet undefined subgroup of meningiomas.
Methods:
Effects of DCT on proliferation and viability was analyzed in primary meningioma cells by immunofluorescence and MTT assays, and cases were classified as drug responders and non-responders. Molecular preconditions for efficacy were analyzed using immunofluorescence for Ki67, DNMT1, and five oncogenes (TRIM58, FAM84B, ELOVL2, MAL2, LMO3) previously found to be differentially methylated after DCT exposition, as well as by genome-wide DNA methylation analyses.
Results:
Efficacy of DCT (10µM) was found in eight (62%) of 13 meningioma cell lines 48 h after drug exposition (p < .05). DCT significantly reduced DNMT1 expression in all but two cell lines, and median ΔDNMT1 reduction 48 h after drug exposition was lower in DCT-resistant (-11.1%) than in DCT-sensitive (-50.5%, p = .030) cells. Rates of cell lines responsive to DCT exposition distinctly decreased to 25% after 72 h. No significant correlation of the patients´ age, sex, histological subtype, location of the paternal tumor, expression of Ki67, DNMT1 or the analyzed oncogenes with treatment response was found (p > .05, each). DCT efficacy was further independent of the methylation class and global DNA methylation of the paternal tumor.
Conclusion:
Early effects of DCT in meningiomas are strongly related with DNMT1 expression, while clinical, histological, and molecular predictors for efficacy are sparse. Kinetics of drug efficacy might indicate necessity of repeated exposition and encourage further analyses.
Insights
Decitabine (DCT) shows efficacy in 62% of meningioma cell lines, with early responses linked to DNMT1 expression. Further research is needed to identify predictors for sustained DCT treatment effectiveness in meningiomas.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Meningiomas lack effective chemotherapies.
- Decitabine (DCT), a DNA methyltransferase (DNMT) inhibitor, shows preclinical promise in a subset of meningiomas.
Purpose of the Study:
- To investigate the efficacy of decitabine (DCT) in treating meningioma cells.
- To identify molecular predictors for DCT response in meningiomas.
Main Methods:
- Primary meningioma cells were treated with DCT.
- Proliferation and viability were assessed using immunofluorescence and MTT assays.
- Gene expression (Ki67, DNMT1, oncogenes) and DNA methylation were analyzed.
Main Results:
- DCT (10µM) was effective in 62% of meningioma cell lines at 48 hours.
- DNMT1 expression reduction was significantly lower in DCT-resistant cells.
- Efficacy decreased to 25% by 72 hours, with no correlation to clinical or molecular factors.
Conclusions:
- Early DCT efficacy in meningiomas correlates with DNMT1 expression.
- Clinical and molecular predictors for sustained response are limited.
- Drug kinetics suggest potential benefit from repeated DCT administration.
