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5`aza-dC demethylation of three short term cultured glioblastomas

ABSTRACT: Glioblastoma, the most aggressive and least treatable form of malignant glioma, is the most common human brain tumor. Although many regions of allelic loss occur in glioblastomas, relatively few tumor suppressor genes have been found mutated at such loci. To address the possibility that epigenetic alterations are an alternative means of glioblastoma gene inactivation, we coupled pharmacological manipulation of methylation with gene profiling to identify potential methylation-regulated, tumor-related genes. Triplicates of three short-term cultured glioblastomas were exposed to 5μM 5-aza-dC for 96 hours followed by cRNA hybridization to an oligonucleotide microarray (Affymetrix U133A). We based candidate gene selection on bioinformatics, RT-PCR, bisulfite sequencing, methylation-specific PCR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Two genes identified in this manner, RUNX3 and Testin (TES), were subsequently shown to harbor frequent tumor-specific epigenetic alterations in primary glioblastomas. This overall approach therefore provides a powerful means to identify candidate tumor suppressor genes for subsequent evaluation and may lead to the identification of genes whose epigenetic dysregulation is integral to glioblastoma tumorigenesis. Keywords: expression profile following global demethylation

ORGANISM(S): Homo sapiens

PROVIDER: GSE4717 | GEO | 2006/11/03

SECONDARY ACCESSION(S): PRJNA95605

REPOSITORIES: GEO

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Transcription profiling of human short term cultured glioblastoma cell lines treated with 5-aza-2-deoxycitidine to investigate if epigenetic alterations are an alternative means of glioblastoma gene inactivation

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