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Homogenous Subgroups of Atypical Meningiomas Defined Using Oncogenic Signatures

25 Pages Posted: 7 Dec 2018

See all articles by Zsolt Zador

Zsolt Zador

University of Toronto - Division of Neurosurgery

Alexander Landry

University of Toronto - Division of Neurosurgery

Ashirbani Saha

University of Toronto - Division of Neurosurgery

Michael D. Cusimano

University of Toronto - Division of Neurosurgery

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Abstract

Meningiomas are the most common brain tumor with a prevalence of 3% in the population. Histological grading of meningiomas (1 through 3) has a major role in determining treatment choice and predicting outcome. While largely indolent grade 1 and the highly aggressive grade 3 meningiomas as considered mostly homogenous in clinical behavior, atypical or grade 2 meningiomas have highly diverse biological properties. Our aim was to identify homogenous subgroups of atypical meningiomas with the working hypothesis that these subgroups would share features with grade 1 and grade 3 counterparts. We carried out systems level analysis by gene module discovery using co-expression networks on the transcriptomics of 212 meningiomas. The newly identified subgroups were characterized in terms of recurrence rate and overlapping biological processes in gene ontology. We were able to reclassify 33 of 46 atypical meningiomas (72%) into a benign "grade 1-like" (14/46) and malignant "grade 3-like" (19/46) subgroup based on oncogenic signatures. Recurrence rates of "Grade 1-like" and "grade 3- like" tumors was 0% and 72% respectively. These two new subgroups showed similar recurrence rates and concordant biological processes with the respected grades. Our findings help resolve the heterogeneity/uncertainty around atypical meningioma biology and identify subgroups more homogenous than in prior studies. These results may help reshape prediction, follow-up planning, treatment decisions and recruitment protocols for future and ongoing clinical trials. The findings demonstrate the conceptual advantage of systems biology approaches and underpin the utility of molecular signatures as complements to histological grading.

Funding Statement: Zsolt Zador: National Institute for Health Research, Academic Clinical Lectureship.

Declaration of Interests: Authors declare no conflict of interest.

Ethics Approval Statement: The authors state: "The study relies entirely on publicly available data."

Keywords: meningioma; co-expression networks; WHO grade; recurrence

Suggested Citation

Zador, Zsolt and Landry, Alexander and Saha, Ashirbani and Cusimano, Michael D., Homogenous Subgroups of Atypical Meningiomas Defined Using Oncogenic Signatures (November 30, 2018). Available at SSRN: https://ssrn.com/abstract=3296635

Zsolt Zador (Contact Author)

University of Toronto - Division of Neurosurgery ( email )

Toronto
Canada

Alexander Landry

University of Toronto - Division of Neurosurgery

Toronto
Canada

Ashirbani Saha

University of Toronto - Division of Neurosurgery

Toronto
Canada

Michael D. Cusimano

University of Toronto - Division of Neurosurgery

Toronto
Canada

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