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Transcriptome signatures associated with meningioma progression.

Angela N Viaene1,2, Bo Zhang3, Maria Martinez-Lage1,4

  • 1Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Acta Neuropathologica Communications
|May 2, 2019
PubMed
Summary

Aggressive brain tumors (meningiomas) show molecular differences linked to progression. Key genes like GREM2 and specific snoRNAs are reduced in higher-grade meningiomas, offering insights into tumor development.

Keywords:
Immune infiltrationMeningiomaProgressionTranscriptomesnoRNAs

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Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Meningiomas are the most common primary adult brain tumors.
  • While most are benign (WHO grade I), 20% are aggressive (WHO grade II/III), necessitating complex management.
  • Mechanisms driving meningioma progression and aggressive tumor formation are poorly understood.

Purpose of the Study:

  • To investigate the molecular differences in meningiomas of varying grades.
  • To identify genes and molecular pathways associated with meningioma progression.
  • To explore novel fusion transcripts and immune microenvironment variations in meningiomas.

Main Methods:

  • RNA sequencing (RNA-seq) was employed to profile the transcriptomes of grade I, II, and III meningiomas.
  • Bioinformatic analyses were conducted to identify differentially expressed genes and fusion transcripts.
  • Tumor immune microenvironment characteristics were analyzed in relation to histopathological grade.

Main Results:

  • Molecular profiles of progressing grade I meningiomas differ significantly from non-progressing ones.
  • GREM2 (BMP pathway regulator) and snoRNAs SNORA46/SNORA48 were found to be significantly reduced in meningioma progression.
  • Novel fusion transcripts were identified, with non-progressing grade I tumors exhibiting a higher number compared to other grades.
  • Distinct tumor immune microenvironment features correlate with meningioma histopathological grade.

Conclusions:

  • Specific molecular alterations, including reduced GREM2 and snoRNAs, are associated with meningioma progression.
  • Fusion transcripts may serve as potential biomarkers for meningioma behavior.
  • The tumor immune microenvironment varies with histopathological grade, suggesting its role in meningioma pathogenesis.