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Published on: September 7, 2017
DNA methylation profile of human dura and leptomeninges
Andrea Daniela Maier1,2, Steffan Noe Christiansen3, Jeppe Haslund-Vinding1
1Department of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Abstract:
Healthy meninges are used as control tissue in meningioma studies usually without specification of the exact meningeal layer or macroanatomical origin but the DNA methylation profile of human meninges has not been investigated on a macroanatomical level. We undertook a proof-of-principle analysis to determine whether (1) meningeal tissues show sufficiently homogenous DNA methylation profiles to function as normal control tissue without further specification and (2) if previously described location-specific molecular signatures of meningiomas correspond to region-specific DNA methylation patterns. Dura mater and arachnoid membrane specimens were dissected from 5 anatomical locations in 2 fresh human cadavers and analyzed with the Illumina Infinium MethylationEPIC array. Dura and leptomeninges showed marked differences in global DNA methylation patterns and between rostral and caudal anatomical locations. These differences did not reflect known anatomical predilection of meningioma molecular signatures. The highest numbers of differentially methylated probes were annotated to DIPC2 and FOXP1. Samples from foramen magnum showed hypomethylation of TFAP2B compared to those from remaining locations. Thus, the DNA methylation profiles of human meninges are heterogenous in terms of meningeal layer and anatomical location. The potential variability of DNA methylation data from meningiomas should be considered in studies using meningeal controls.
Insights
Human meninges exhibit diverse DNA methylation patterns across anatomical locations and layers. This heterogeneity challenges their use as uniform control tissue in meningioma research, necessitating careful consideration of origin.
Area of Science:
- Neuroscience
- Genomics
- Epigenetics
Background:
- Meningioma studies often use healthy meninges as control tissue without specifying anatomical origin or layer.
- The macroanatomical DNA methylation profile of human meninges remains largely uninvestigated.
- Understanding meningeal methylation is crucial for interpreting molecular signatures in meningioma research.
Purpose of the Study:
- To assess the homogeneity of DNA methylation profiles in human meninges for use as control tissue.
- To investigate if regional DNA methylation patterns in meninges correlate with known meningioma molecular signatures.
- To explore macroanatomical variations in meningeal DNA methylation.
Main Methods:
- Dissection of dura mater and arachnoid membrane specimens from five anatomical locations in human cadavers.
- Analysis of DNA methylation using the Illumina Infinium MethylationEPIC array.
- Comparative analysis of methylation profiles between different meningeal layers and anatomical regions.
Main Results:
- Significant differences in global DNA methylation patterns were observed between the dura mater and leptomeninges.
- Marked variations in DNA methylation were found between rostral and caudal anatomical locations.
- Differential methylation probes were notably associated with DIPC2 and FOXP1 genes.
- Hypomethylation of TFAP2B was observed in samples from the foramen magnum region.
Conclusions:
- Human meningeal DNA methylation profiles are heterogeneous, varying by meningeal layer and anatomical location.
- The observed heterogeneity does not align with established anatomical predilections of meningioma molecular signatures.
- Researchers should consider the inherent variability of meningeal DNA methylation when using them as control tissue in meningioma studies.
