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Published on: January 9, 2019
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.
Abstract:
To identify gene expression profiles associated with human meningiomas of different World Health Organization (WHO) malignancy grades, we analyzed 30 tumors (13 benign meningiomas, WHO grade I; 12 atypical meningiomas, WHO grade II; 5 anaplastic meningiomas, WHO grade III) for the expression of 2,600 genes using cDNA-microarray technology. Receiver operator curve (ROC) analysis with a cutoff value of 45% selection probability identified 37 genes with decreased and 27 genes with increased expression in atypical and anaplastic meningiomas, compared to benign meningiomas. Supervised classification of the tumors did not reveal specific expression patterns representative of each WHO grade. However, anaplastic meningiomas could be distinguished from benign meningiomas by differential expression of a distinct set of genes, including several ones associated with cell cycle regulation and proliferation. Investigation of potential correlations between microarray expression data and genomic aberrations, detected by comparative genomic hybridization (CGH), demonstrated that losses on chromosomes 10 and 14 were associated with distinct expression profiles, including increased expression of several genes related to the insulin-like growth factor (IGF) (IGF2, IGFBP3 and AKT3) or wingless (WNT) (CTNNB1, CDK5R1, ENC1 and CCND1) pathways. Taken together, our microarray-based expression profiling revealed interesting novel candidate genes and pathways that may contribute to meningioma progression.
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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