Multiple approaches converge on three biological subtypes of meningioma and extract new insights from published studies

Abstract

One-fifth of meningiomas classified as benign by World Health Organization (WHO) histopathological grading will behave malignantly. To better diagnose these tumors, several groups turned to DNA methylation, whereas we combined RNA-sequencing (RNA-seq) and cytogenetics. Both approaches were more accurate than histopathology in identifying aggressive tumors, but whether they revealed similar tumor types was unclear. We therefore performed unbiased DNA methylation, RNA-seq, and cytogenetic profiling on 110 primary meningiomas WHO grade I and II). Each technique distinguished the same three groups (two benign and one malignant) as our previous molecular classification; integrating these methods into one classifier further improved accuracy. Computational modeling revealed strong correlations between transcription and cytogenetic changes, particularly loss of chromosome 1p, in malignant tumors. Applying our classifier to data from previous studies also resolved certain anomalies entailed by grouping tumors by WHO grade. Accurate classification will therefore elucidate meningioma biology as well as improve diagnosis and prognosis.

Potential Molecular Mechanisms of Recurrent and Progressive Meningiomas: A Review of the Latest Literature

“…A 2022 study classified meningiomas into three methylation groups, similar to the study by Sahm and co-workers ( 102 ), and showed that DNA methylation is more accurate than histopathology in identifying high-risk tumors and is closely correlated with gene expression in meningiomas ( 118 ). This study further compared the predictive accuracy of DNA methylation with that of RNA-sequencing and cytogenetics and found a strong concordance between these groups.…”

“…This study further compared the predictive accuracy of DNA methylation with that of RNA-sequencing and cytogenetics and found a strong concordance between these groups. The authors also demonstrated that both DNA promoter methylation and copy-number variability correlated with differential gene expression ( 118 ). Further, a recent study analyzed four types of alterations together, namely DNA somatic copy-number aberrations, DNA somatic point mutations, DNA methylation, and messenger RNA abundance, and found that these could be classified into four groups (M1–4) owing to distinct biology as follows: immunogenic (M1), benign NF2 wild-type (M2), hypermetabolic (M3), and proliferative (M4) ( 12 ) ( Table 2 ) .…”

P53 Suppressor Gene Tissue Microarray-based Protein Expression Analysis in Meningiomas

“…In these aggressive phenotypes, genetic analyses have already confirmed the presence of gross chromosomal and also specific gene imbalances (gains, rearrangements and intra-or inter-translocations, frame-shift deletions/insertions, in-frame fusions or point-driver mutations) (18)(19)(20). Numerical imbalances in chromosomes including chromosome 22, fragment deletions on chromosome 1p and 2q33-q35, specific regional chromosome 6p21-p22, 13q33, 17 and 19 amplifications have been also detected and reported (21)(22)(23)(24)(25). Furthermore, a variety of single nucleotide polymorphisms have been also recognized (26).…”

Recent advances in the molecular prognostication of meningiomas

“…Integrated use of DNA methylation, RNA sequencing, and cytogenetic profiling by Patel et al on 110 grade 1 and II meningiomas according to the 2016 WHO classification system revealed two benign and one malignant tumor group closely resembling the previously established type A, B, and C classifications (103). Methylation analysis further distinguished these groups as tumors with balanced methylation (Meth 1), hypomethylation (Meth 2), and hypermethylation (Meth 3) (103).…”