Molecular signatures define two main classes of meningiomas.
BACKGROUND
Meningiomas are common brain tumors that are classified into three World Health Organization grades (benign, atypical and malignant) and are molecularly ill-defined tumors. The purpose of this study was identify molecular signatures unique to the different grades of meningiomas and to unravel underlying molecular mechanisms driving meningioma tumorigenesis.


RESULTS
We have used a combination of gene expression microarrays and array comparative genomic hybridization (aCGH) to show that meningiomas of all three grades fall into two main molecular groups designated 'low-proliferative' and 'high-proliferative' meningiomas. While all benign meningiomas fall into the low-proliferative group and all malignant meningiomas fall into the high-proliferative group, atypical meningiomas distribute into either one of these groups. High-proliferative atypical meningiomas had an elevated median MIB-1 labeling index and a greater frequency of copy number aberrations (CNAs) compared to low-proliferative atypical meningiomas. Additionally, losses on chromosome 6q, 9p, 13 and 14 were found exclusively in the high-proliferative meningiomas. We have identified genes that distinguish benign low-proliferative meningiomas from malignant high-proliferative meningiomas and have found that gain of cell-proliferation markers and loss of components of the transforming growth factor-beta signaling pathway were the major molecular mechanisms that distinguish these two groups.


CONCLUSIONS
Collectively, our data suggests that atypical meningiomas are not a molecularly distinct group but are similar to either benign or malignant meningiomas. It is anticipated that identified molecular and CNA markers will potentially be more accurate prognostic markers of meningiomas.
Carvalho
Lucia Helena
LH
Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, CA-94143, USA. luhe.carvalho@gmail.com
Smirnov
Ivan
I
Baia
Gilson S
GS
Modrusan
Zora
Z
Smith
Justin S
JS
Jun
Peter
P
Costello
Joseph F
JF
McDermott
Michael W
MW
Vandenberg
Scott R
SR
Lal
Anita
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D008579:Meningioma / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods*