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DNA Methylation in the Malignant Transformation of Meningiomas

Meningiomas are central nervous system tumors that originate from the meningeal coverings of the brain and spinal cord. Most meningiomas are pathologically benign or atypical, but 3–5% display malignant features. Despite previous studies on benign and atypical meningiomas, the key molecular pathways...

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Autores principales: Gao, Fan, Shi, Lingling, Russin, Jonathan, Zeng, Liyun, Chang, Xiao, He, Shuhan, Chen, Thomas C., Giannotta, Steven L., Weisenberger, Daniel J., Zada, Gabriel, Mack, William J., Wang, Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551961/
https://www.ncbi.nlm.nih.gov/pubmed/23349797
http://dx.doi.org/10.1371/journal.pone.0054114
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author Gao, Fan
Shi, Lingling
Russin, Jonathan
Zeng, Liyun
Chang, Xiao
He, Shuhan
Chen, Thomas C.
Giannotta, Steven L.
Weisenberger, Daniel J.
Zada, Gabriel
Mack, William J.
Wang, Kai
author_facet Gao, Fan
Shi, Lingling
Russin, Jonathan
Zeng, Liyun
Chang, Xiao
He, Shuhan
Chen, Thomas C.
Giannotta, Steven L.
Weisenberger, Daniel J.
Zada, Gabriel
Mack, William J.
Wang, Kai
author_sort Gao, Fan
collection PubMed
description Meningiomas are central nervous system tumors that originate from the meningeal coverings of the brain and spinal cord. Most meningiomas are pathologically benign or atypical, but 3–5% display malignant features. Despite previous studies on benign and atypical meningiomas, the key molecular pathways involved in malignant transformation remain to be determined, as does the extent of epigenetic alteration in malignant meningiomas. In this study, we explored the landscape of DNA methylation in ten benign, five atypical and four malignant meningiomas. Compared to the benign tumors, the atypical and malignant meningiomas demonstrate increased global DNA hypomethylation. Clustering analysis readily separates malignant from atypical and benign tumors, implicating that DNA methylation patterns may serve as diagnostic biomarkers for malignancy. Genes with hypermethylated CpG islands in malignant meningiomas (such as HOXA6 and HOXA9) tend to coincide with the binding sites of polycomb repressive complexes (PRC) in early developmental stages. Most genes with hypermethylated CpG islands at promoters are suppressed in malignant and benign meningiomas, suggesting the switching of gene silencing machinery from PRC binding to DNA methylation in malignant meningiomas. One exception is the MAL2 gene that is highly expressed in benign group and silenced in malignant group, representing de novo gene silencing induced by DNA methylation. In summary, our results suggest that malignant meningiomas have distinct DNA methylation patterns compared to their benign and atypical counterparts, and that the differentially methylated genes may serve as diagnostic biomarkers or candidate causal genes for malignant transformation.
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spelling pubmed-35519612013-01-24 DNA Methylation in the Malignant Transformation of Meningiomas Gao, Fan Shi, Lingling Russin, Jonathan Zeng, Liyun Chang, Xiao He, Shuhan Chen, Thomas C. Giannotta, Steven L. Weisenberger, Daniel J. Zada, Gabriel Mack, William J. Wang, Kai PLoS One Research Article Meningiomas are central nervous system tumors that originate from the meningeal coverings of the brain and spinal cord. Most meningiomas are pathologically benign or atypical, but 3–5% display malignant features. Despite previous studies on benign and atypical meningiomas, the key molecular pathways involved in malignant transformation remain to be determined, as does the extent of epigenetic alteration in malignant meningiomas. In this study, we explored the landscape of DNA methylation in ten benign, five atypical and four malignant meningiomas. Compared to the benign tumors, the atypical and malignant meningiomas demonstrate increased global DNA hypomethylation. Clustering analysis readily separates malignant from atypical and benign tumors, implicating that DNA methylation patterns may serve as diagnostic biomarkers for malignancy. Genes with hypermethylated CpG islands in malignant meningiomas (such as HOXA6 and HOXA9) tend to coincide with the binding sites of polycomb repressive complexes (PRC) in early developmental stages. Most genes with hypermethylated CpG islands at promoters are suppressed in malignant and benign meningiomas, suggesting the switching of gene silencing machinery from PRC binding to DNA methylation in malignant meningiomas. One exception is the MAL2 gene that is highly expressed in benign group and silenced in malignant group, representing de novo gene silencing induced by DNA methylation. In summary, our results suggest that malignant meningiomas have distinct DNA methylation patterns compared to their benign and atypical counterparts, and that the differentially methylated genes may serve as diagnostic biomarkers or candidate causal genes for malignant transformation. Public Library of Science 2013-01-22 /pmc/articles/PMC3551961/ /pubmed/23349797 http://dx.doi.org/10.1371/journal.pone.0054114 Text en © 2013 Gao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gao, Fan
Shi, Lingling
Russin, Jonathan
Zeng, Liyun
Chang, Xiao
He, Shuhan
Chen, Thomas C.
Giannotta, Steven L.
Weisenberger, Daniel J.
Zada, Gabriel
Mack, William J.
Wang, Kai
DNA Methylation in the Malignant Transformation of Meningiomas
title DNA Methylation in the Malignant Transformation of Meningiomas
title_full DNA Methylation in the Malignant Transformation of Meningiomas
title_fullStr DNA Methylation in the Malignant Transformation of Meningiomas
title_full_unstemmed DNA Methylation in the Malignant Transformation of Meningiomas
title_short DNA Methylation in the Malignant Transformation of Meningiomas
title_sort dna methylation in the malignant transformation of meningiomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551961/
https://www.ncbi.nlm.nih.gov/pubmed/23349797
http://dx.doi.org/10.1371/journal.pone.0054114
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