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DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis.
Felix Sahm1, Daniel Schrimpf2, Damian Stichel3
1Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
DNA methylation profiling identifies six distinct meningioma classes, improving tumor classification and prognosis prediction beyond the current WHO grading system. This molecular approach offers better patient stratification for treatment decisions.
Area of Science:
- Neuro-oncology
- Molecular pathology
- Genomics
Background:
- The World Health Organization (WHO) classification categorizes meningiomas into 15 subtypes with grades I, II, and III based solely on histology.
- Current grading criteria are subjective and lack molecular markers, leading to limitations in prognostic accuracy and arbitrary judgments.
- There is a need for a more objective and biologically relevant classification system for meningiomas.
Purpose of the Study:
- To comprehensively characterize the molecular genetic landscape of meningiomas.
- To identify biologically and clinically relevant subgroups of meningiomas using DNA methylation profiling.
- To develop a more accurate classification system for meningioma prognosis and treatment stratification.
Main Methods:
- Genome-wide DNA methylation patterns of 497 meningiomas were analyzed using unsupervised clustering.
- Methylation classes were further characterized by DNA copy number analysis, mutational profiling, and RNA sequencing.
- A DNA methylation-based classification was compared to the WHO classification using the Brier prediction score in an independent cohort.
Main Results:
- DNA methylation profiling clearly segregated meningiomas from other skull tumors and identified six distinct, clinically relevant methylation classes.
- This molecular classification demonstrated superior accuracy in predicting tumor recurrence and prognosis compared to the WHO classification.
- The new classification identified high-risk WHO grade I tumors and lower-risk WHO grade II tumors, validated in an independent cohort.
Conclusions:
- DNA methylation-based classification provides a more objective and powerful tool for stratifying meningioma patients.
- This approach enhances the prediction of tumor recurrence and patient prognosis, surpassing the current WHO grading system.
- Methylation-based classification holds significant relevance for the future diagnosis and personalized treatment of meningiomas.
