Candidate genes for the progression of malignant gliomas identified by microarray analysis.
Malignant astrocytomas of World Health Organization (WHO) grade III or IV have a reduced median survival time, and possible pathways have been described for the progression of anaplastic astrocytomas and glioblastomas, but the molecular basis of malignant astrocytoma progression is still poorly understood. Microarray analysis provides the chance to accelerate studies by comparison of the expression of thousands of genes in these tumours and consequently identify targeting genes. We compared the transcriptional profile of 4,608 genes in tumours of 15 patients including 6 anaplastic astrocytomas (WHO grade III) and 9 glioblastomas (WHO grade IV) using microarray analysis. The microarray data were corroborated by real-time reverse transcription-polymerase chain reaction analysis of two selected genes. We identified 166 gene alterations with a fold change of 2 and higher whose mRNA levels differed (absolute value of the t statistic of 1.96) between the two malignant glioma groups. Further analyses confirmed same transcription directions for Olig2 and IL-13Ralpha2 in anaplastic astrocytomas as compared to glioblastomas. Microarray analyses with a close binary question reveal numerous interesting candidate genes, which need further histochemical testing after selection for confirmation. IL-13Ralpha2 and Olig2 have been identified and confirmed to be interesting candidate genes whose differential expression likely plays a role in malignant progression of astrocytomas.
Bozinov
Oliver
O
Department of Neurosurgery, Philipps-University Marburg, Baldingerstrasse, 35033 Marburg, Germany. bozinov@med.uni-marburg.de
Köhler
Sylvia
S
Samans
Birgit
B
Benes
Ludwig
L
Miller
Dorothea
D
Ritter
Markus
M
Sure
Ulrich
U
Bertalanffy
Helmut
H
D001254:Astrocytoma / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D018450:Disease Progression; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051792:Basic Helix-Loop-Helix Proteins; D053663:Interleukin-13 Receptor alpha2 Subunit; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C405708:OLIG2 protein, human