Microarray analysis reveals down-regulation of the tumour suppressor gene WWOX and up-regulation of the oncogene TYMS in intracranial sporadic meningiomas.
BACKGROUND
In order to investigate pathways that may influence on tumour development in meningiomas, we performed high throughput microarray analysis of the RNA expression and DNA copy number of 22 WHO grade I and five WHO grade II meningiomas. Since meningiomas derive from arachnoid cap cells, we used samples from four patients operated for arachnoid cysts as control tissue.


RESULTS
The expression of the tumour suppressor gene WW containing oxidoreductase (WWOX) was down-regulated, and the thymidylate synthase (TYMS) oncogene was up-regulated in all meningiomas as compared to arachnoid cysts. Unsupervised RNA cluster analysis showed that fibrous meningiomas gathered in two clusters, and thus were more homogeneous than the other meningiomas. The other histological subgroups could not be linked to any uniform gene expression signatures. Rearrangements were most abundant on chromosomes 1 and 22, but were identified on all except chromosome 16. The fibrous and mixed meningiomas generally had chromosomal deletions. Duplications were more frequent in the meningothelial meningiomas. WHO grade II meningiomas had increased chromosomal instability.


CONCLUSIONS
Decreased expression of the WWOX tumour suppressor gene and increased expression of the TYMS oncogene may be of importance for the development of human intracranial meningiomas. We have identified several genes (BMPR1B, DMD, RAMP1) with expression signatures specific for fibrous meningiomas. CGH analysis revealed distinct chromosomal patterns in relation to the histological subtypes of the meningiomas.
Aarhus
Mads
M
Section for Neurosurgery, Department of Surgical Sciences, University of Bergen, Bergen, Norway. mads.aarhus@kir.uib.no
Bruland
Ove
O
Bredholt
Geir
G
Lybaek
Helle
H
Husebye
Eystein S
ES
Krossnes
Bård K
BK
Vedeler
Christian
C
Wester
Knut
K
Lund-Johansen
Morten
M
Knappskog
Per M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D016515:Genes, Neurofibromatosis 2; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics / Q000378:metabolism*; D008579:Meningioma / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000074584:WW Domain-Containing Oxidoreductase
D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; D013940:Thymidylate Synthase