GSTM1 null genotype underpins recurrence of NF2 meningiomas

IntroductionMeningiomas are the most common primary central nervous system (CNS) tumor in adults, comprising one-third of all primary adult CNS tumors. Although several recent publications have identified molecular alterations in meningioma including characteristic mutations, copy number alterations...

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Main Authors: Anthony C. Johnson, Erdyni N. Tsitsikov, Khanh P. Phan, Jeffrey A. Zuccato, Andrew M. Bauer, Christopher S. Graffeo, Sanaa Hameed, Tressie M. Stephens, Yufeng Liu, Gavin P. Dunn, Alla V. Tsytsykova, Pamela S. Jones, Ian F. Dunn
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2024.1506708/full
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author Anthony C. Johnson
Anthony C. Johnson
Erdyni N. Tsitsikov
Khanh P. Phan
Jeffrey A. Zuccato
Andrew M. Bauer
Christopher S. Graffeo
Sanaa Hameed
Tressie M. Stephens
Yufeng Liu
Gavin P. Dunn
Alla V. Tsytsykova
Pamela S. Jones
Ian F. Dunn
author_facet Anthony C. Johnson
Anthony C. Johnson
Erdyni N. Tsitsikov
Khanh P. Phan
Jeffrey A. Zuccato
Andrew M. Bauer
Christopher S. Graffeo
Sanaa Hameed
Tressie M. Stephens
Yufeng Liu
Gavin P. Dunn
Alla V. Tsytsykova
Pamela S. Jones
Ian F. Dunn
author_sort Anthony C. Johnson
collection DOAJ
description IntroductionMeningiomas are the most common primary central nervous system (CNS) tumor in adults, comprising one-third of all primary adult CNS tumors. Although several recent publications have identified molecular alterations in meningioma including characteristic mutations, copy number alterations, and gene expression signatures, our understanding of the drivers of meningioma recurrence is limited.ObjectiveTo identify gene expression signatures of 1p-22q-NF2- meningioma recurrence, with concurrent biallelic inactivation of NF2 and loss of chr1p that are heterogenous but enriched for recurrent meningiomas.MethodsTranscriptomic alterations present in recurrent versus primary 1p-22q-NF2- meningiomas were identified using RNA sequencing (RNA-seq) data in a clinically annotated cohort.ResultsRecurrent 1p-22q-NF2- meningiomas were enriched for a newly identified GSTM1 null genotype compared to primary meningiomas that showed variable GSTM1 expression and independent external validation was performed.ConclusionsThe GSTM1 null genotype is a novel biomarker of 1p-22q-NF2- meningioma recurrence that resolves heterogeneity in existing meningioma subtypes and may be used to guide future clinical management decisions on extent of treatment to improve patient outcomes.
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spelling doaj-art-ae07ec22ef2b4062b73fde6b7b0ce77c2025-08-20T02:50:19ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-12-011410.3389/fonc.2024.15067081506708GSTM1 null genotype underpins recurrence of NF2 meningiomasAnthony C. Johnson0Anthony C. Johnson1Erdyni N. Tsitsikov2Khanh P. Phan3Jeffrey A. Zuccato4Andrew M. Bauer5Christopher S. Graffeo6Sanaa Hameed7Tressie M. Stephens8Yufeng Liu9Gavin P. Dunn10Alla V. Tsytsykova11Pamela S. Jones12Ian F. Dunn13Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesIntroductionMeningiomas are the most common primary central nervous system (CNS) tumor in adults, comprising one-third of all primary adult CNS tumors. Although several recent publications have identified molecular alterations in meningioma including characteristic mutations, copy number alterations, and gene expression signatures, our understanding of the drivers of meningioma recurrence is limited.ObjectiveTo identify gene expression signatures of 1p-22q-NF2- meningioma recurrence, with concurrent biallelic inactivation of NF2 and loss of chr1p that are heterogenous but enriched for recurrent meningiomas.MethodsTranscriptomic alterations present in recurrent versus primary 1p-22q-NF2- meningiomas were identified using RNA sequencing (RNA-seq) data in a clinically annotated cohort.ResultsRecurrent 1p-22q-NF2- meningiomas were enriched for a newly identified GSTM1 null genotype compared to primary meningiomas that showed variable GSTM1 expression and independent external validation was performed.ConclusionsThe GSTM1 null genotype is a novel biomarker of 1p-22q-NF2- meningioma recurrence that resolves heterogeneity in existing meningioma subtypes and may be used to guide future clinical management decisions on extent of treatment to improve patient outcomes.https://www.frontiersin.org/articles/10.3389/fonc.2024.1506708/fullmeningiomarecurrentCNS tumorstranscriptome profilinggene expressionNF2
spellingShingle Anthony C. Johnson
Anthony C. Johnson
Erdyni N. Tsitsikov
Khanh P. Phan
Jeffrey A. Zuccato
Andrew M. Bauer
Christopher S. Graffeo
Sanaa Hameed
Tressie M. Stephens
Yufeng Liu
Gavin P. Dunn
Alla V. Tsytsykova
Pamela S. Jones
Ian F. Dunn
GSTM1 null genotype underpins recurrence of NF2 meningiomas
Frontiers in Oncology
meningioma
recurrent
CNS tumors
transcriptome profiling
gene expression
NF2
title GSTM1 null genotype underpins recurrence of NF2 meningiomas
title_full GSTM1 null genotype underpins recurrence of NF2 meningiomas
title_fullStr GSTM1 null genotype underpins recurrence of NF2 meningiomas
title_full_unstemmed GSTM1 null genotype underpins recurrence of NF2 meningiomas
title_short GSTM1 null genotype underpins recurrence of NF2 meningiomas
title_sort gstm1 null genotype underpins recurrence of nf2 meningiomas
topic meningioma
recurrent
CNS tumors
transcriptome profiling
gene expression
NF2
url https://www.frontiersin.org/articles/10.3389/fonc.2024.1506708/full
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