Molecular profiling of pediatric meningiomas shows tumor characteristics distinct from adult meningiomas

Abstract

In contrast to adults, meningiomas are uncommon tumors in childhood and adolescence. Whether adult and pediatric meningiomas differ on a molecular level is unclear. Here we report detailed genomic analyses of 37 pediatric meningiomas by sequencing and DNA methylation profiling. Histologically, the series was dominated by meningioma subtypes with aggressive behavior, with 70% of patients suffering from WHO grade II or III meningiomas. The most frequent cytogenetic aberrations were loss of chromosomes 22 (23/37 [62%]), 1 (9/37 [24%]), 18 (7/37 [19%]), and 14 (5/37 [14%]). Tumors with NF2 alterations exhibited overall increased chromosomal instability. Unsupervised clustering of DNA methylation profiles revealed separation into three groups: designated group 1 composed of clear cell and papillary meningiomas, whereas group 2A comprised predominantly atypical meningiomas and group 2B enriched for rare high-grade subtypes (rhabdoid, chordoid). Meningiomas from NF2 patients clustered exclusively within groups 1 and 2A. When compared with a dataset of 105 adult meningiomas, the pediatric meningiomas largely grouped separately. Targeted panel DNA sequencing of 34 tumors revealed frequent NF2 alterations, while other typical alterations found in adult non-NF2 tumors were absent. These data demonstrate that pediatric meningiomas are characterized by molecular features distinct from adult tumors.

A new amplicon‐based gene panel for next generation sequencing characterization of meningiomas

“…The rare mutations in SMARCB1 [6] and SMARCE1 , the latter known to be restricted to clear cell meningiomas and frequently found in younger patients [20, 29], were both observed only at frequencies around 1% in our series. The single TERT promoter mutation occurred in a high‐grade (atypical) meningioma, in accordance with literature, where the activating mutations of the promoter, C228T and C250T, are largely restricted to WHO grades II and III, where they occur at moderate frequencies around 4%–5% (grade II) and 16%–20% (grade III) [21, 30].…”

Impact of epigenetics on human health and possible tool for remediation

“…Several attributes to this covalent modification landscape include regulation of transcription, accessibility of the DNA template, DNA repair signaling, etc. A fine balance maintains the normal profile of the cell and an imbalance can be associated with development of diseased states including cancer, neuronal disorder, impaired DNA repair, exposure associated disorders [6,27,42,51]. In the present issue, Dhar et al [12] and Banerjee et al [2] outlines some of the major aspects of DNA methylation and how it affects gene expression and development of neuronal disorder like autism.…”

Review of meningioma diagnosis and management

“…Accounting for approximately one-third of all primary central nervous system tumors in adult patients, meningiomas are the most prevalent primary brain tumor [1,2]. With the median age of diagnosis being 65,36.6% of all adult brain tumors are diagnosed as meningiomas, and as few as 3-5% of pediatric primary brain tumors are believed to be meningiomas [2,3].…”

“…Accounting for approximately one-third of all primary central nervous system tumors in adult patients, meningiomas are the most prevalent primary brain tumor [1,2]. With the median age of diagnosis being 65,36.6% of all adult brain tumors are diagnosed as meningiomas, and as few as 3-5% of pediatric primary brain tumors are believed to be meningiomas [2,3]. With the exception of rare high-grade variants and pediatric cases, primary brain meningiomas are more common in female patients at an incidence rate of 3:1 compared to males [4,5].…”