Evidence map›Paper›PMID 27158275›Full record

ArticleClinical epigenetics2016

MGMT promoter methylation determined by HRM in comparison to MSP and pyrosequencing for predicting high-grade glioma response.

Olivier J Switzeny, Markus Christmann, Mirjam Renovanz, Alf Giese, Clemens Sommer, Bernd Kaina

Open access · goldAbstract readComparative Study
In one paragraph

Article in Clinical epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 2 pooled it
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Olivier J SwitzenyDepartment of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany.
Markus ChristmannDepartment of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany.
Mirjam RenovanzDepartment of Neurosurgery, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
Alf GieseDepartment of Neurosurgery, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
Clemens SommerDepartment of Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
Bernd KainaDepartment of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany.
Johannes Gutenberg University Mainz · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) causes resistance of cancer cells to alkylating agents and, therefore, is a well-established predictive marker for high-grade gliomas that are routinely treated with alkylating drugs. Since MGMT is highly epigenetically regulated, the MGMT promoter methylation status is taken as an indicator of MGMT silencing, predicting the outcome of glioma therapy. MGMT promoter methylation is usually determined by methylation specific PCR (MSP), which is a labor intensive and error-prone method often used semi-quantitatively. Searching for alternatives, we used closed-tube high resolution melt (HRM) analysis, which is a quantitative method, and compared it with MSP and pyrosequencing regarding its predictive value.

resultsWe analyzed glioblastoma cell lines with known MGMT activity and formalin-fixed samples from IDH1 wild-type high-grade glioma patients (WHO grade III/IV) treated with radiation and temozolomide by HRM, MSP, and pyrosequencing. The data were compared as to progression-free survival (PFS) and overall survival (OS) of patients exhibiting the methylated and unmethylated MGMT status. A promoter methylation cut-off level relevant for PFS and OS was determined. In a multivariate Cox regression model, methylation of MGMT promoter of high-grade gliomas analyzed by HRM, but not MSP, was found to be an independent predictive marker for OS. Univariate Kaplan-Meier analyses revealed for PFS and OS a significant and better discrimination between methylated and unmethylated tumors when quantitative HRM was used instead of MSP.

conclusionsCompared to MSP and pyrosequencing, the HRM method is simple, cost effective, highly accurate and fast. HRM is at least equivalent to pyrosequencing in quantifying the methylation level. It is superior in predicting PFS and OS of high-grade glioma patients compared to MSP and, therefore, can be recommended being used routinely for determination of the MGMT status of gliomas.

Indexed as

DNA MethylationAgedAged, 80 and overDNA Modification MethylasesDNA Repair EnzymesFemaleGlioblastomaGliomaHumansMaleMiddle AgedPolymerase Chain ReactionPromoter Regions, GeneticReproducibility of ResultsSensitivity and SpecificitySequence Analysis, DNADNA Modification MethylasesDNA Repair EnzymesMGMT protein, humanTumor Suppressor ProteinsAlkyltransferaseBrain tumorsEpigenetic silencingGlioblastomaIDH1MGMTPromoter methylationTemozolomide

Identifiers

PMID27158275
PMCPMC4858829
OpenAlexW2345717877

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.