Microarray-based gene expression profiling of benign, atypical and anaplastic meningiomas identifies novel genes

Gunnar Wrobel1, Peter Roerig, Felix Kokocinski

  • 1Division of Molecular Genetics, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.

Insights

Gene expression profiles in human meningiomas reveal distinct patterns linked to malignancy. Anaplastic tumors show altered cell cycle and proliferation genes, with chromosomal losses correlating to specific pathway activations.

Area of Science:

  • Neuro-oncology
  • Molecular biology
  • Genomics

Background:

  • Meningiomas are tumors arising from the meninges.
  • World Health Organization (WHO) grading classifies meningiomas into I, II, and III based on malignancy.
  • Understanding gene expression differences across grades is crucial for prognosis.

Purpose of the Study:

  • To identify gene expression profiles associated with different World Health Organization (WHO) malignancy grades of human meningiomas.
  • To explore correlations between gene expression, genomic aberrations, and tumor progression.

Main Methods:

  • Analysis of gene expression in 30 meningioma tumors (13 grade I, 12 grade II, 5 grade III) using cDNA-microarray technology (2,600 genes).
  • Receiver operator curve (ROC) analysis to identify differentially expressed genes.
  • Comparative genomic hybridization (CGH) to detect genomic aberrations.

Main Results:

  • Identified 37 downregulated and 27 upregulated genes in atypical and anaplastic meningiomas compared to benign ones.
  • Anaplastic meningiomas distinguished from benign by differential expression of cell cycle and proliferation genes.
  • Losses on chromosomes 10 and 14 correlated with distinct expression profiles, including activation of insulin-like growth factor (IGF) and wingless (WNT) pathways.

Conclusions:

  • Microarray-based expression profiling reveals novel candidate genes and pathways involved in meningioma progression.
  • Specific gene expression patterns are associated with higher-grade meningiomas.
  • Genomic aberrations influence gene expression profiles, potentially driving tumor aggressiveness.

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