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Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis

BACKGROUND: Cranial radiation therapy is essential in treating many pediatric cancers, especially brain tumors; however, its use comes with the risk of developing second malignancies. Cranial radiation-induced gliomas (RIGs) are aggressive high-grade tumors with a dismal prognosis, for which no stan...

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Autores principales: Whitehouse, Jacqueline P, Howlett, Meegan, Federico, Aniello, Kool, Marcel, Endersby, Raelene, Gottardo, Nicholas G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633655/
https://www.ncbi.nlm.nih.gov/pubmed/34859225
http://dx.doi.org/10.1093/noajnl/vdab109
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author Whitehouse, Jacqueline P
Howlett, Meegan
Federico, Aniello
Kool, Marcel
Endersby, Raelene
Gottardo, Nicholas G
author_facet Whitehouse, Jacqueline P
Howlett, Meegan
Federico, Aniello
Kool, Marcel
Endersby, Raelene
Gottardo, Nicholas G
author_sort Whitehouse, Jacqueline P
collection PubMed
description BACKGROUND: Cranial radiation therapy is essential in treating many pediatric cancers, especially brain tumors; however, its use comes with the risk of developing second malignancies. Cranial radiation-induced gliomas (RIGs) are aggressive high-grade tumors with a dismal prognosis, for which no standard therapy exists. A definitive molecular signature for RIGs has not yet been established. We sought to address this gap by performing a systematic review and meta-analysis of the molecular features of cranial RIGs. METHODS: A systematic review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles and case reports that described molecular analyses of cranial radiation-induced high-grade gliomas were identified and evaluated, and data extracted for collation. RESULTS: Of 1727 records identified, 31 were eligible, containing 102 unique RIGs with molecular data. The most frequent genetic alterations in RIGs included PDGFRA or TP53 mutations, PDGFRA or CDK4 amplifications, and CDKN2A deletion, along with 1q gain, 1p loss and 13q loss. Of note, mutations in ACVR1, EGFR, H3F3A, HIST1H3B, HIST1H3C, IDH2, SMARCB1 or the TERT promoter were not observed. A comparative analysis revealed that RIGs are molecularly distinct from most other astrocytomas and gliomas and instead align most closely with the pedGBM_RTK1 subgroup of pediatric glioblastoma. CONCLUSIONS: This comprehensive analysis highlights the major molecular features of RIGs, demonstrates their molecular distinction from many other astrocytomas and gliomas, and reveals potential genetic drivers and therapeutic targets for this currently fatal disease.
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spelling pubmed-86336552021-12-01 Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis Whitehouse, Jacqueline P Howlett, Meegan Federico, Aniello Kool, Marcel Endersby, Raelene Gottardo, Nicholas G Neurooncol Adv Reviews BACKGROUND: Cranial radiation therapy is essential in treating many pediatric cancers, especially brain tumors; however, its use comes with the risk of developing second malignancies. Cranial radiation-induced gliomas (RIGs) are aggressive high-grade tumors with a dismal prognosis, for which no standard therapy exists. A definitive molecular signature for RIGs has not yet been established. We sought to address this gap by performing a systematic review and meta-analysis of the molecular features of cranial RIGs. METHODS: A systematic review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles and case reports that described molecular analyses of cranial radiation-induced high-grade gliomas were identified and evaluated, and data extracted for collation. RESULTS: Of 1727 records identified, 31 were eligible, containing 102 unique RIGs with molecular data. The most frequent genetic alterations in RIGs included PDGFRA or TP53 mutations, PDGFRA or CDK4 amplifications, and CDKN2A deletion, along with 1q gain, 1p loss and 13q loss. Of note, mutations in ACVR1, EGFR, H3F3A, HIST1H3B, HIST1H3C, IDH2, SMARCB1 or the TERT promoter were not observed. A comparative analysis revealed that RIGs are molecularly distinct from most other astrocytomas and gliomas and instead align most closely with the pedGBM_RTK1 subgroup of pediatric glioblastoma. CONCLUSIONS: This comprehensive analysis highlights the major molecular features of RIGs, demonstrates their molecular distinction from many other astrocytomas and gliomas, and reveals potential genetic drivers and therapeutic targets for this currently fatal disease. Oxford University Press 2021-08-12 /pmc/articles/PMC8633655/ /pubmed/34859225 http://dx.doi.org/10.1093/noajnl/vdab109 Text en © The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Reviews
Whitehouse, Jacqueline P
Howlett, Meegan
Federico, Aniello
Kool, Marcel
Endersby, Raelene
Gottardo, Nicholas G
Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis
title Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis
title_full Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis
title_fullStr Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis
title_full_unstemmed Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis
title_short Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis
title_sort defining the molecular features of radiation-induced glioma: a systematic review and meta-analysis
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633655/
https://www.ncbi.nlm.nih.gov/pubmed/34859225
http://dx.doi.org/10.1093/noajnl/vdab109
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