Do we really know who has an MGMT methylated glioma? Results of an international survey regarding use of MGMT analyses for glioma
© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology..
BACKGROUND: Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.
METHODS: We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.
RESULTS: The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1-3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.
CONCLUSION: Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Neuro-oncology practice - 7(2020), 1 vom: 01. Jan., Seite 68-76 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Malmström, Annika [VerfasserIn] |
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| Links: |
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| Themen: |
Glioma |
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| Anmerkungen: |
Date Revised 12.04.2022 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1093/nop/npz039 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM306200503 |
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| 520 | |a © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. | ||
| 520 | |a BACKGROUND: Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results | ||
| 520 | |a METHODS: We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff | ||
| 520 | |a RESULTS: The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1-3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing | ||
| 520 | |a CONCLUSION: Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a MGMT testing | |
| 650 | 4 | |a glioma | |
| 650 | 4 | |a international consensus guidelines | |
| 650 | 4 | |a international survey | |
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| 700 | 1 | |a Kristensen, Bjarne Winther |e verfasserin |4 aut | |
| 700 | 1 | |a Hovey, Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Henriksson, Roger |e verfasserin |4 aut | |
| 700 | 1 | |a Söderkvist, Peter |e verfasserin |4 aut | |
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