Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction.
Diffuse astrocytoma of World Health Organization (WHO) grade II has an inherent tendency to spontaneously progress to anaplastic astrocytoma (WHO grade III) and/or glioblastoma (WHO grade IV). The molecular basis of astrocytoma progression is still poorly understood, in particular with respect to the progression-associated changes at the mRNA level. Therefore, we compared the transcriptional profile of approximately 6800 genes in primary WHO grade II gliomas and corresponding recurrent high-grade (WHO grade III or IV) gliomas from eight patients using oligonucleotide-based microarray analysis. We identified 66 genes whose mRNA levels differed significantly (P < 0.01, > or =2-fold change) between the primary and recurrent tumors. The microarray data were corroborated by real-time reverse transcription-polymerase chain reaction analysis of 12 selected genes, including 7 genes with increased expression and 5 genes with reduced expression on progression. In addition, the expression of these 12 genes was determined in an independent series of 43 astrocytic gliomas (9 diffuse astrocytomas, 10 anaplastic astrocytomas, 17 primary, and 7 secondary glioblastomas). These analyses confirmed that the transcript levels of nine of the selected genes (COL4A2, FOXM1, MGP, TOP2A, CENPF, IGFBP4, VEGFA, ADD3, and CAMK2G) differed significantly in WHO grade II astrocytomas as compared to anaplastic astrocytomas and/or glioblastomas. Thus, we identified and validated a set of interesting candidate genes whose differential expression likely plays a role in astrocytoma progression.
van den Boom
Jörg
J
Department of Neuropathology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
Wolter
Marietta
M
Kuick
Rork
R
Misek
David E
DE
Youkilis
Andrew S
AS
Wechsler
Daniel S
DS
Sommer
Clemens
C
Reifenberger
Guido
G
Hanash
Samir M
SM
D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000235:genetics; D003199:Computer Systems; D018450:Disease Progression; D016326:Extracellular Matrix Proteins; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D000097568:Matrix Gla Protein
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D000097568:Matrix Gla Protein; C107585:FOXM1 protein, human