MGMT promoter methylation status in anaplastic meningiomas

Brokinkel, Benjamin; Fischer, Bernhard R.; Peetz-Dienhart, Susanne; Ebel, Heinrich; Sepehrnia, Abolghassem; Rama, B.; Albert, Friedrich K.; Stummer, Walter; Paulus, Werner; Hasselblatt, Martin

doi:10.1007/s11060-010-0202-0

Cited by 12 publications

(4 citation statements)

References 8 publications

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“…In the past, several studies focused on investigating promoter methylation mainly using a targeted approach for a limited number of genes [4,6–8,11,30,14,15,34,38,47]. With time, molecular advances allowed interrogation at a larger number of CpG loci [35] culminating with the methylation assays from Illumina (27k and 450k) interrogating approximately 27.000 and 450.000 CpG loci [74,21].…”

Section: Discussionmentioning

confidence: 99%

Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma

Olar

Wani

Wilson³

et al. 2017

Acta Neuropathol

141

115

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Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. Methylation profiles of meningioma and their clinical implications are not well understood. We hypothesized that aggressive meningiomas have unique DNA methylation patterns that could be used to better stratify patient management. Samples (n=140) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised modeling on a training set (n=89) identified 2 molecular methylation subgroups of meningioma (MM) with significantly different recurrence free survival (RFS) times between the groups: a prognostically unfavorable subgroup (MM-UNFAV) and a prognostically favorable subgroup (MM-FAV). This finding was validated in the remaining 51 samples and led to a baseline meningioma methylation classifier (bMMC) defined by 283 CpG loci (283-bMMC). To further optimize a recurrence predictor, probes subsumed within the baseline classifier were subject to additional modeling using a similar training/validation approach, leading to a 64-CpG loci meningioma methylation predictor (64-MMP). After adjustment for relevant clinical variables [WHO grade, mitotic index, Simpson grade, sex, location, and copy number aberrations (CNA)] multivariable analyses for RFS showed that the baseline methylation classifier was not significant (p=0.0793). The methylation predictor however was significantly associated with tumor recurrence (p<0.0001). CNA were extracted from the 450k intensity profiles. Tumor samples in the MM-UNFAV subgroup showed an overall higher proportion of CNAs compared to the MM-FAV subgroup tumors and the CNAs were complex in nature. CNAs in the MM-UNFAV subgroup included recurrent losses of 1p, 6q, 14q and 18q, and gain of 1q, all of which were previously identified as indicators of poor outcome. In conclusion, our analyses demonstrate robust DNA methylation signatures in meningioma that correlate with CNAs and stratify patients by recurrence risk.

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Section: Discussionmentioning

confidence: 99%

Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma

Olar

Wani

Wilson³

et al. 2017

Acta Neuropathol

141

115

View full text Add to dashboard Cite

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“…In all of the 40 patients, DNA from representative tumor material was obtained by isolation and bisulfite conversion (EZ DNA Methylation Gold‐kit; Zymo Research, Orange, CA, USA). Methylation‐specific PCR was performed according to standard procedures . Since no correlation between MGMT promoter methylation status and the other parameters chosen in this study, that is, tumor volume, ITSS score, and involvement of the SVZ, could be observed, a detailed illustration was dismissed in the manuscript.…”

Section: Methodsmentioning

confidence: 99%

Variations of ITSS‐Morphology and their Relationship to Location and Tumor Volume in Patients with Glioblastoma

Fahrendorf

Heßelmann

Schwindt

et al. 2015

Journal of Neuroimaging

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“…2A-D). O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was determined using methylation-specific polymerase chain reaction (PCR) 8 and was found to be negative. Postoperative MRI revealed subtotal tumor resection with small contrast-enhancing remnants at the upper parts of the resection cavity (►Fig.…”

Section: Clinical Presentationmentioning

confidence: 99%

Cerebellar Anaplastic Astrocytoma in an Adult with Neurofibromatosis Type 1: Case Report and Review of Literature

Brokinkel

Schober

Ewelt

et al. 2013

J Neurol Surg A Cent Eur Neurosurg

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A literature search yielded only one previously published case of an AA in a 9-year-old girl with NF1. Tumor control after resection was achieved in both patients; however, the patient in the mentioned report received radiation instead of temozolomide. In spite of different adjuvant therapies, tumor control for at least 16 months was achieved in both published cases. Thus, even though the role of adjuvant treatment options remains to be further elucidated, surgery is the appropriate therapy in these uncommon tumors providing mass reduction and histological diagnosis as well as tumor control.

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MGMT promoter methylation status in anaplastic meningiomas

Cited by 12 publications

References 8 publications

Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma

Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma

Variations of ITSS‐Morphology and their Relationship to Location and Tumor Volume in Patients with Glioblastoma

Cerebellar Anaplastic Astrocytoma in an Adult with Neurofibromatosis Type 1: Case Report and Review of Literature

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