Molecular description of meningeal solitary fibrous tumors/hemangiopericytomas compared to meningiomas: two completely separate entities.

Caroline Apra,Karima Mokhtari,Delphine Guillemot,Michel Kalamarides,Gaëlle Pierron,Corinne Bouvier,Eléonore Frouin

doi:10.1007/s11060-021-03830-7

Abstract

Meningeal solitary fibrous tumors (SFT), like all SFT, are defined by NAB2-STAT6 fusion and share clinicopathologic similarities with meningiomas, the most frequent meningeal tumors. Our aim is to establish the molecular identity of meningeal SFT and seek molecular prognostic factors. RNA sequencing and whole exome sequencing were performed in STAT6-positive SFT and grade 2-3 meningiomas, and data concerning other soft tissues tumors was obtained from the local database. Uniform manifold approximation and projection, individual gene expression and Gene Set Enrichment Analysis were performed. RNA clustering shows that SFT share a common molecular signature, different from any other type of tumoral tissue. Meningeal SFT aggregate with other SFT, with no clinical or histological subgroup. Comparison of genes expressions suggests significant over-expressions of ZIC2, ZIC3, ZIC5, GABBR2, TP53 in CNS-SFT. The pathogenic TP53 c.743G>T variant, previously undescribed in SFT, was found in one sample of meningeal SFT during malignant progression. Meningeal SFT are molecular counterparts of extra-meningeal SFT, completely separate from meningiomas. They might develop from the same tissues and benefit from the same treatments as SFT.

Highlights

Meningeal solitary fibrous tumors (SFT), like all SFT, are defined by NAB2-STAT6 fusion and share clinicopathologic similarities with meningiomas, the most frequent meningeal tumors
With the list of genes of 5% internal quantile range (IQR) variation, we looked for enrichment of pathways (GSEA, Gene Set Enrichment Analysis open access software GSEA, Broad Institute, USA) with gene sets v.7.1 and genes annotations Human_Illumina_HumanHT_12_v3_MSigDB.v7.1.chip
According to VarSome predictors, only one pathogenic variant was identified during histological malignant progression, in one case, the pathogenic TP53 c.743G>T, and RNA sequencing showed that TP53 was expressed in the sample

Summary

Introduction

Meningeal solitary fibrous tumors (SFT), like all SFT, are defined by NAB2-STAT6 fusion and share clinicopathologic similarities with meningiomas, the most frequent meningeal tumors. Meningeal or central nervous system Solitary Fibrous Tumors (CNS-SFT), formerly known as hemangiopericytomas [3,4], share the same molecular signature as SFT that develop in other organs, the NAB2-STAT6 fusion [5], and are classified in grades 1,2 and 3 [3]. CNS-SFT are clinically and radiologically very close to meningiomas, which represent the most frequent meningeal tumor type, and resemble in particular grade 2-3 meningiomas [6]. The clinical course of CNSSFT is varied and unpredictable, which makes it difficult to tailor adjuvant treatments after surgery: up to 10% of patients develop metastases and 50% recur within 10 years, even in grade 1 cases [9,10]

Objectives

Methods

Results

Conclusion