Molecular Characterization of Human Meningiomas by Gene Expression Profiling Using High-Density Oligonucleotide Microarrays

摘要

Meningiomas are common central nervous system neoplasms that exhibit remarkably diverse histopathology and biological behavior. Compared to astrocytomas, the most common central nervous system tumor, little is known about the molecular pathways critical for meningioma tumor formation and malignant progression. As an initial step toward characterizing the genetic basis of meningioma pathogenesis, we assessed cancer-related gene expression profiles of nonneoplastic leptomeningeal specimens and human meningiomas of varying World Health Organization (WHO) grade using high-density oligonucleotide microarrays. Although expression profile differences between nonneoplastic and meningioma specimens were readily discernible, the expression profile of a subset of genes could also distinguish WHO grade I from WHO grades II and III tumors. Altered expression levels of several genes identified in this study have been previously noted in meningiomas (eg, growth hormone receptor, IGFBP-7, endothelin receptor A, IGF2). However, we also identified a number of novel genes whose expression was associated with WHO grade and was confirmed by reverse transcriptase-polymerase chain reaction in a larger, independent set of meningeal tumors (>n = 47). This report represents the first gene expression profiling studies of meningiomas and identifies some initial candidate genes that may provide further insights into the genetic basis for meningioma pathogenesis.