Molecular signatures define two main classes of meningiomas

Lucia Helena Carvalho, Ivan Smirnov, Gilson S. Baia, Zora Modrusan, Justin S. Smith, Peter Jun, Joseph F. Costello, Michael W. McDermott, Scott R. VandenBerg, Anita Lal

Research output: Contribution to journalArticle

Abstract

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. Conclusion: 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.

Original languageEnglish (US)
Article number64
JournalMolecular Cancer
Volume6
DOIs
StatePublished - Oct 15 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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    Carvalho, L. H., Smirnov, I., Baia, G. S., Modrusan, Z., Smith, J. S., Jun, P., Costello, J. F., McDermott, M. W., VandenBerg, S. R., & Lal, A. (2007). Molecular signatures define two main classes of meningiomas. Molecular Cancer, 6, [64]. https://doi.org/10.1186/1476-4598-6-64