An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures

Grace Collord; Patrick Tarpey; Natalja Kurbatova; Inigo Martincorena; Sebastian Moran; Manuel Castro; Tibor Nagy; Graham Bignell; Francesco Maura; Matthew D Young; Jorge Berna; Jose M C Tubio; Chris E McMurran; Adam M H Young; Mathijs Sanders; Imran Noorani; Stephen J Price; Colin Watts; Elke Leipnitz; Matthias Kirsch; Gabriele Schackert; Danita Pearson; Abel Devadass; Zvi Ram; V Peter Collins; Kieren Allinson; Michael D Jenkinson; Rasheed Zakaria; Khaja Syed; C Oliver Hanemann; Jemma Dunn; Michael W McDermott; Ramez W Kirollos; George S Vassiliou; Manel Esteller; Sam Behjati; Alvis Brazma; Thomas Santarius; Ultan McDermott

doi:10.1038/s41598-018-31659-0

An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures

Grace Collord, Patrick Tarpey, Natalja Kurbatova, Inigo Martincorena, Sebastian Moran, Manuel Castro, Tibor Nagy, Graham Bignell, Francesco Maura, Matthew D Young, Jorge Berna, Jose M C Tubio, Chris E McMurran, Adam M H Young, Mathijs Sanders, Imran Noorani, Stephen J Price, Colin Watts, Elke Leipnitz, Matthias KirschGabriele Schackert, Danita Pearson, Abel Devadass, Zvi Ram, V Peter Collins, Kieren Allinson, Michael D Jenkinson, Rasheed Zakaria, Khaja Syed, C Oliver Hanemann, Jemma Dunn, Michael W McDermott, Ramez W Kirollos, George S Vassiliou, Manel Esteller, Sam Behjati, Alvis Brazma, Thomas Santarius, Ultan McDermott

Cancer and Genomic Sciences

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Abstract

Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of distinct molecular subgroups that were associated with diametrically opposed survival outcomes. Relative to lower grade meningiomas, anaplastic tumors harbored frequent driver mutations in SWI/SNF complex genes, which were confined to the poor prognosis subgroup. Aggressive disease was further characterised by transcriptional evidence of increased PRC2 activity, stemness and epithelial-to-mesenchymal transition. Our analyses discern biologically distinct variants of anaplastic meningioma with prognostic and therapeutic significance.

Original language	English
Article number	13537
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-31659-0
Publication status	Published - 10 Sept 2018

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Collord_et_al_An_integrated_genomic_analysis_Scientific_Reports_2018
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Collord, G., Tarpey, P., Kurbatova, N., Martincorena, I., Moran, S., Castro, M., Nagy, T., Bignell, G., Maura, F., Young, M. D., Berna, J., Tubio, J. M. C., McMurran, C. E., Young, A. M. H., Sanders, M., Noorani, I., Price, S. J., Watts, C., Leipnitz, E., ... McDermott, U. (2018). An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures. Scientific Reports, 8(1), Article 13537. https://doi.org/10.1038/s41598-018-31659-0

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title = "An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures",

abstract = "Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of distinct molecular subgroups that were associated with diametrically opposed survival outcomes. Relative to lower grade meningiomas, anaplastic tumors harbored frequent driver mutations in SWI/SNF complex genes, which were confined to the poor prognosis subgroup. Aggressive disease was further characterised by transcriptional evidence of increased PRC2 activity, stemness and epithelial-to-mesenchymal transition. Our analyses discern biologically distinct variants of anaplastic meningioma with prognostic and therapeutic significance.",

author = "Grace Collord and Patrick Tarpey and Natalja Kurbatova and Inigo Martincorena and Sebastian Moran and Manuel Castro and Tibor Nagy and Graham Bignell and Francesco Maura and Young, {Matthew D} and Jorge Berna and Tubio, {Jose M C} and McMurran, {Chris E} and Young, {Adam M H} and Mathijs Sanders and Imran Noorani and Price, {Stephen J} and Colin Watts and Elke Leipnitz and Matthias Kirsch and Gabriele Schackert and Danita Pearson and Abel Devadass and Zvi Ram and Collins, {V Peter} and Kieren Allinson and Jenkinson, {Michael D} and Rasheed Zakaria and Khaja Syed and Hanemann, {C Oliver} and Jemma Dunn and McDermott, {Michael W} and Kirollos, {Ramez W} and Vassiliou, {George S} and Manel Esteller and Sam Behjati and Alvis Brazma and Thomas Santarius and Ultan McDermott",

year = "2018",

month = sep,

day = "10",

doi = "10.1038/s41598-018-31659-0",

language = "English",

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Collord, G, Tarpey, P, Kurbatova, N, Martincorena, I, Moran, S, Castro, M, Nagy, T, Bignell, G, Maura, F, Young, MD, Berna, J, Tubio, JMC, McMurran, CE, Young, AMH, Sanders, M, Noorani, I, Price, SJ, Watts, C, Leipnitz, E, Kirsch, M, Schackert, G, Pearson, D, Devadass, A, Ram, Z, Collins, VP, Allinson, K, Jenkinson, MD, Zakaria, R, Syed, K, Hanemann, CO, Dunn, J, McDermott, MW, Kirollos, RW, Vassiliou, GS, Esteller, M, Behjati, S, Brazma, A, Santarius, T & McDermott, U 2018, 'An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures', Scientific Reports, vol. 8, no. 1, 13537. https://doi.org/10.1038/s41598-018-31659-0

TY - JOUR

T1 - An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures

AU - Collord, Grace

AU - Tarpey, Patrick

AU - Kurbatova, Natalja

AU - Martincorena, Inigo

AU - Moran, Sebastian

AU - Castro, Manuel

AU - Nagy, Tibor

AU - Bignell, Graham

AU - Maura, Francesco

AU - Young, Matthew D

AU - Berna, Jorge

AU - Tubio, Jose M C

AU - McMurran, Chris E

AU - Young, Adam M H

AU - Sanders, Mathijs

AU - Noorani, Imran

AU - Price, Stephen J

AU - Watts, Colin

AU - Leipnitz, Elke

AU - Kirsch, Matthias

AU - Schackert, Gabriele

AU - Pearson, Danita

AU - Devadass, Abel

AU - Ram, Zvi

AU - Collins, V Peter

AU - Allinson, Kieren

AU - Jenkinson, Michael D

AU - Zakaria, Rasheed

AU - Syed, Khaja

AU - Hanemann, C Oliver

AU - Dunn, Jemma

AU - McDermott, Michael W

AU - Kirollos, Ramez W

AU - Vassiliou, George S

AU - Esteller, Manel

AU - Behjati, Sam

AU - Brazma, Alvis

AU - Santarius, Thomas

AU - McDermott, Ultan

PY - 2018/9/10

Y1 - 2018/9/10

N2 - Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of distinct molecular subgroups that were associated with diametrically opposed survival outcomes. Relative to lower grade meningiomas, anaplastic tumors harbored frequent driver mutations in SWI/SNF complex genes, which were confined to the poor prognosis subgroup. Aggressive disease was further characterised by transcriptional evidence of increased PRC2 activity, stemness and epithelial-to-mesenchymal transition. Our analyses discern biologically distinct variants of anaplastic meningioma with prognostic and therapeutic significance.

AB - Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of distinct molecular subgroups that were associated with diametrically opposed survival outcomes. Relative to lower grade meningiomas, anaplastic tumors harbored frequent driver mutations in SWI/SNF complex genes, which were confined to the poor prognosis subgroup. Aggressive disease was further characterised by transcriptional evidence of increased PRC2 activity, stemness and epithelial-to-mesenchymal transition. Our analyses discern biologically distinct variants of anaplastic meningioma with prognostic and therapeutic significance.

U2 - 10.1038/s41598-018-31659-0

DO - 10.1038/s41598-018-31659-0

M3 - Article

C2 - 30202034

VL - 8

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 13537

ER -

An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures

Abstract

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