The Prognostic Value of Methylation Signatures and <i>NF2</i> Mutations in Atypical Meningiomas
<i>Background</i>: Due to the solely subjective histopathological assessment, the WHO 2016 classification of human meningiomas is subject to interobserver variation. Consequently, the need for more reliable and objective markers are highly needed. The aim of this pilot study was to apply...
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MDPI AG
2021-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/6/1262 |
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| author | Rahmina Meta Henning B. Boldt Bjarne W. Kristensen Felix Sahm Wenche Sjursen Sverre H. Torp |
| author_facet | Rahmina Meta Henning B. Boldt Bjarne W. Kristensen Felix Sahm Wenche Sjursen Sverre H. Torp |
| author_sort | Rahmina Meta |
| collection | DOAJ |
| description | <i>Background</i>: Due to the solely subjective histopathological assessment, the WHO 2016 classification of human meningiomas is subject to interobserver variation. Consequently, the need for more reliable and objective markers are highly needed. The aim of this pilot study was to apply genome-wide DNA methylation analysis on a series of atypical meningiomas to evaluate the practical utility of this approach, examine whether prognostic subclasses are achieved and investigate whether there is an association between the methylation subclasses with poor prognosis and time to recurrence. <i>NF1/2</i> mutation analyses were also performed to explore the prognostic value of such mutations in these atypical meningiomas. <i>Methods</i>: Twenty intracranial WHO grade II atypical meningiomas from adult patients were included. They consisted of 10 cases with recurrence (group I), and 10 cases without recurrence (<i>group II</i>). The formalin-fixed and paraffin-embedded tissues underwent standardized genome-wide DNA methylation analysis, and the profiles were matched with the reference library and tumor classifier from Heidelberg. <i>NF1/2</i> somatic mutation analyses were performed using the CNSv1panel from Düsseldorf. <i>Results</i>: Eighteen out of 20 cases matched to the meningioma class using the common brain tumor classifier (v11b4). Four of these cases matched to a methylation subclass related to a prognostic subgroup based on a cut-off of 0.9. <i>NF2</i> mutations were detected in 55% of cases across both groups, and the most prominent copy number alterations were chromosomal losses of 22q, 1p and 14q. No significant <i>NF1</i> mutations were identified. <i>Conclusions</i>: Genome-wide DNA methylation profiling represents a useful tool in the diagnostics of meningiomas, however, methodological adjustments need to be addressed. |
| first_indexed | 2024-03-10T13:17:30Z |
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| language | English |
| last_indexed | 2024-03-10T13:17:30Z |
| publishDate | 2021-03-01 |
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| series | Cancers |
| spelling | doaj.art-84d6f192bdad404ead5ec258c55efff42023-11-21T10:17:04ZengMDPI AGCancers2072-66942021-03-01136126210.3390/cancers13061262The Prognostic Value of Methylation Signatures and <i>NF2</i> Mutations in Atypical MeningiomasRahmina Meta0Henning B. Boldt1Bjarne W. Kristensen2Felix Sahm3Wenche Sjursen4Sverre H. Torp5Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, NorwayDepartment of Pathology, Odense University Hospital, 5000 Odense, DenmarkDepartment of Pathology, Odense University Hospital, 5000 Odense, DenmarkDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, GermanyDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway<i>Background</i>: Due to the solely subjective histopathological assessment, the WHO 2016 classification of human meningiomas is subject to interobserver variation. Consequently, the need for more reliable and objective markers are highly needed. The aim of this pilot study was to apply genome-wide DNA methylation analysis on a series of atypical meningiomas to evaluate the practical utility of this approach, examine whether prognostic subclasses are achieved and investigate whether there is an association between the methylation subclasses with poor prognosis and time to recurrence. <i>NF1/2</i> mutation analyses were also performed to explore the prognostic value of such mutations in these atypical meningiomas. <i>Methods</i>: Twenty intracranial WHO grade II atypical meningiomas from adult patients were included. They consisted of 10 cases with recurrence (group I), and 10 cases without recurrence (<i>group II</i>). The formalin-fixed and paraffin-embedded tissues underwent standardized genome-wide DNA methylation analysis, and the profiles were matched with the reference library and tumor classifier from Heidelberg. <i>NF1/2</i> somatic mutation analyses were performed using the CNSv1panel from Düsseldorf. <i>Results</i>: Eighteen out of 20 cases matched to the meningioma class using the common brain tumor classifier (v11b4). Four of these cases matched to a methylation subclass related to a prognostic subgroup based on a cut-off of 0.9. <i>NF2</i> mutations were detected in 55% of cases across both groups, and the most prominent copy number alterations were chromosomal losses of 22q, 1p and 14q. No significant <i>NF1</i> mutations were identified. <i>Conclusions</i>: Genome-wide DNA methylation profiling represents a useful tool in the diagnostics of meningiomas, however, methodological adjustments need to be addressed.https://www.mdpi.com/2072-6694/13/6/1262brain tumorsmeningiomasprognosisdiagnosismethylation profilingmolecular genetics |
| spellingShingle | Rahmina Meta Henning B. Boldt Bjarne W. Kristensen Felix Sahm Wenche Sjursen Sverre H. Torp The Prognostic Value of Methylation Signatures and <i>NF2</i> Mutations in Atypical Meningiomas Cancers brain tumors meningiomas prognosis diagnosis methylation profiling molecular genetics |
| title | The Prognostic Value of Methylation Signatures and <i>NF2</i> Mutations in Atypical Meningiomas |
| title_full | The Prognostic Value of Methylation Signatures and <i>NF2</i> Mutations in Atypical Meningiomas |
| title_fullStr | The Prognostic Value of Methylation Signatures and <i>NF2</i> Mutations in Atypical Meningiomas |
| title_full_unstemmed | The Prognostic Value of Methylation Signatures and <i>NF2</i> Mutations in Atypical Meningiomas |
| title_short | The Prognostic Value of Methylation Signatures and <i>NF2</i> Mutations in Atypical Meningiomas |
| title_sort | prognostic value of methylation signatures and i nf2 i mutations in atypical meningiomas |
| topic | brain tumors meningiomas prognosis diagnosis methylation profiling molecular genetics |
| url | https://www.mdpi.com/2072-6694/13/6/1262 |
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