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Genomic markers of recurrence risk in atypical meningioma following gross total resection

BACKGROUND: Meningiomas are the most common primary central nervous system (CNS) tumor in adults and CNS World Health Organization grade 2 (atypical) meningiomas show an intermediate risk of recurrence/progression. Molecular parameters are needed to better inform management following gross total res...

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Autores principales: Vaubel, Rachael A, Kumar, Rahul, Weiskittel, Taylor M, Jenkins, Sarah, Dasari, Surendra, Uhm, Joon H, Lachance, Daniel H, Brown, Paul D, Van Gompel, Jamie J, Jenkins, Robert B, Kipp, Benjamin R, Sukov, William R, Giannini, Caterina, Johnson, Derek R, Raghunathan, Aditya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950854/
https://www.ncbi.nlm.nih.gov/pubmed/36845294
http://dx.doi.org/10.1093/noajnl/vdad004
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author Vaubel, Rachael A
Kumar, Rahul
Weiskittel, Taylor M
Jenkins, Sarah
Dasari, Surendra
Uhm, Joon H
Lachance, Daniel H
Brown, Paul D
Van Gompel, Jamie J
Jenkins, Robert B
Kipp, Benjamin R
Sukov, William R
Giannini, Caterina
Johnson, Derek R
Raghunathan, Aditya
author_facet Vaubel, Rachael A
Kumar, Rahul
Weiskittel, Taylor M
Jenkins, Sarah
Dasari, Surendra
Uhm, Joon H
Lachance, Daniel H
Brown, Paul D
Van Gompel, Jamie J
Jenkins, Robert B
Kipp, Benjamin R
Sukov, William R
Giannini, Caterina
Johnson, Derek R
Raghunathan, Aditya
author_sort Vaubel, Rachael A
collection PubMed
description BACKGROUND: Meningiomas are the most common primary central nervous system (CNS) tumor in adults and CNS World Health Organization grade 2 (atypical) meningiomas show an intermediate risk of recurrence/progression. Molecular parameters are needed to better inform management following gross total resection (GTR). METHODS: We performed comprehensive genomic analysis of tumor tissue from 63 patients who underwent radiologically confirmed GTR of a primary grade 2 meningioma, including a CLIA-certified target next-generation sequencing panel (n = 61), chromosomal microarray (n = 63), genome-wide methylation profiling (n = 62), H3K27me3 immunohistochemistry (n = 62), and RNA-sequencing (n = 19). Genomic features were correlated with long-term clinical outcomes (median follow-up: 10 years) using Cox proportional hazards regression modeling and published molecular prognostic signatures were evaluated. RESULTS: The presence of specific copy number variants (CNVs), including -1p, -10q, -7p, and -4p, was the strongest predictor of decreased recurrence-free survival (RFS) within our cohort (P < .05). NF2 mutations were frequent (51%) but did not show a significant association with RFS. DNA methylation-based classification assigned tumors to DKFZ Heidelberg benign (52%) or intermediate (47%) meningioma subclasses and was not associated with RFS. H3K27 trimethylation (H3K27me3) was unequivocally lost in 4 tumors, insufficient for RFS analysis. Application of published integrated histologic/molecular grading systems did not improve prediction of recurrence risk over the presence of -1p or -10q alone. CONCLUSIONS: CNVs are strong predictors of RFS in grade 2 meningiomas following GTR. Our study supports incorporation of CNV profiling into clinical evaluation to better guide postoperative patient management, which can be readily implemented using existing, clinically validated technologies.
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spelling pubmed-99508542023-02-25 Genomic markers of recurrence risk in atypical meningioma following gross total resection Vaubel, Rachael A Kumar, Rahul Weiskittel, Taylor M Jenkins, Sarah Dasari, Surendra Uhm, Joon H Lachance, Daniel H Brown, Paul D Van Gompel, Jamie J Jenkins, Robert B Kipp, Benjamin R Sukov, William R Giannini, Caterina Johnson, Derek R Raghunathan, Aditya Neurooncol Adv Clinical Investigations BACKGROUND: Meningiomas are the most common primary central nervous system (CNS) tumor in adults and CNS World Health Organization grade 2 (atypical) meningiomas show an intermediate risk of recurrence/progression. Molecular parameters are needed to better inform management following gross total resection (GTR). METHODS: We performed comprehensive genomic analysis of tumor tissue from 63 patients who underwent radiologically confirmed GTR of a primary grade 2 meningioma, including a CLIA-certified target next-generation sequencing panel (n = 61), chromosomal microarray (n = 63), genome-wide methylation profiling (n = 62), H3K27me3 immunohistochemistry (n = 62), and RNA-sequencing (n = 19). Genomic features were correlated with long-term clinical outcomes (median follow-up: 10 years) using Cox proportional hazards regression modeling and published molecular prognostic signatures were evaluated. RESULTS: The presence of specific copy number variants (CNVs), including -1p, -10q, -7p, and -4p, was the strongest predictor of decreased recurrence-free survival (RFS) within our cohort (P < .05). NF2 mutations were frequent (51%) but did not show a significant association with RFS. DNA methylation-based classification assigned tumors to DKFZ Heidelberg benign (52%) or intermediate (47%) meningioma subclasses and was not associated with RFS. H3K27 trimethylation (H3K27me3) was unequivocally lost in 4 tumors, insufficient for RFS analysis. Application of published integrated histologic/molecular grading systems did not improve prediction of recurrence risk over the presence of -1p or -10q alone. CONCLUSIONS: CNVs are strong predictors of RFS in grade 2 meningiomas following GTR. Our study supports incorporation of CNV profiling into clinical evaluation to better guide postoperative patient management, which can be readily implemented using existing, clinically validated technologies. Oxford University Press 2023-01-10 /pmc/articles/PMC9950854/ /pubmed/36845294 http://dx.doi.org/10.1093/noajnl/vdad004 Text en © The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Investigations
Vaubel, Rachael A
Kumar, Rahul
Weiskittel, Taylor M
Jenkins, Sarah
Dasari, Surendra
Uhm, Joon H
Lachance, Daniel H
Brown, Paul D
Van Gompel, Jamie J
Jenkins, Robert B
Kipp, Benjamin R
Sukov, William R
Giannini, Caterina
Johnson, Derek R
Raghunathan, Aditya
Genomic markers of recurrence risk in atypical meningioma following gross total resection
title Genomic markers of recurrence risk in atypical meningioma following gross total resection
title_full Genomic markers of recurrence risk in atypical meningioma following gross total resection
title_fullStr Genomic markers of recurrence risk in atypical meningioma following gross total resection
title_full_unstemmed Genomic markers of recurrence risk in atypical meningioma following gross total resection
title_short Genomic markers of recurrence risk in atypical meningioma following gross total resection
title_sort genomic markers of recurrence risk in atypical meningioma following gross total resection
topic Clinical Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950854/
https://www.ncbi.nlm.nih.gov/pubmed/36845294
http://dx.doi.org/10.1093/noajnl/vdad004
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