Molecular subtypes of glioblastoma are relevant to lower grade glioma.

<h4>Background</h4>Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM) expression and methylation based subtypes to grade II and III gliom...

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Autores principales:	Xiaowei Guan, Jaime Vengoechea, Siyuan Zheng, Andrew E Sloan, Yanwen Chen, Daniel J Brat, Brian Patrick O'Neill, John de Groot, Shlomit Yust-Katz, Wai-Kwan Alfred Yung, Mark L Cohen, Kenneth D Aldape, Steven Rosenfeld, Roeland G W Verhaak, Jill S Barnholtz-Sloan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/11d06f53ffa14d86ae428b8cf35f5a14
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spelling	oai:doaj.org-article:11d06f53ffa14d86ae428b8cf35f5a142021-11-18T08:28:54ZMolecular subtypes of glioblastoma are relevant to lower grade glioma.1932-620310.1371/journal.pone.0091216https://doaj.org/article/11d06f53ffa14d86ae428b8cf35f5a142014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24614622/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM) expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas).<h4>Methods</h4>Gene expression array, single nucleotide polymorphism (SNP) array and clinical data were obtained for 228 GBMs and 176 grade II/II gliomas (GII/III) from the publically available Rembrandt dataset. Two additional datasets with IDH1 mutation status were utilized as validation datasets (one publicly available dataset and one newly generated dataset from MD Anderson). Unsupervised clustering was performed and compared to gene expression subtypes assigned using the Verhaak et al 840-gene classifier. The glioma-CpG Island Methylator Phenotype (G-CIMP) was assigned using prediction models by Fine et al.<h4>Results</h4>Unsupervised clustering by gene expression aligned with the Verhaak 840-gene subtype group assignments. GII/IIIs were preferentially assigned to the proneural subtype with IDH1 mutation and G-CIMP. GBMs were evenly distributed among the four subtypes. Proneural, IDH1 mutant, G-CIMP GII/III s had significantly better survival than other molecular subtypes. Only 6% of GBMs were proneural and had either IDH1 mutation or G-CIMP but these tumors had significantly better survival than other GBMs. Copy number changes in chromosomes 1p and 19q were associated with GII/IIIs, while these changes in CDKN2A, PTEN and EGFR were more commonly associated with GBMs.<h4>Conclusions</h4>GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression.Xiaowei GuanJaime VengoecheaSiyuan ZhengAndrew E SloanYanwen ChenDaniel J BratBrian Patrick O'NeillJohn de GrootShlomit Yust-KatzWai-Kwan Alfred YungMark L CohenKenneth D AldapeSteven RosenfeldRoeland G W VerhaakJill S Barnholtz-SloanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e91216 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaowei Guan Jaime Vengoechea Siyuan Zheng Andrew E Sloan Yanwen Chen Daniel J Brat Brian Patrick O'Neill John de Groot Shlomit Yust-Katz Wai-Kwan Alfred Yung Mark L Cohen Kenneth D Aldape Steven Rosenfeld Roeland G W Verhaak Jill S Barnholtz-Sloan Molecular subtypes of glioblastoma are relevant to lower grade glioma.
description	<h4>Background</h4>Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM) expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas).<h4>Methods</h4>Gene expression array, single nucleotide polymorphism (SNP) array and clinical data were obtained for 228 GBMs and 176 grade II/II gliomas (GII/III) from the publically available Rembrandt dataset. Two additional datasets with IDH1 mutation status were utilized as validation datasets (one publicly available dataset and one newly generated dataset from MD Anderson). Unsupervised clustering was performed and compared to gene expression subtypes assigned using the Verhaak et al 840-gene classifier. The glioma-CpG Island Methylator Phenotype (G-CIMP) was assigned using prediction models by Fine et al.<h4>Results</h4>Unsupervised clustering by gene expression aligned with the Verhaak 840-gene subtype group assignments. GII/IIIs were preferentially assigned to the proneural subtype with IDH1 mutation and G-CIMP. GBMs were evenly distributed among the four subtypes. Proneural, IDH1 mutant, G-CIMP GII/III s had significantly better survival than other molecular subtypes. Only 6% of GBMs were proneural and had either IDH1 mutation or G-CIMP but these tumors had significantly better survival than other GBMs. Copy number changes in chromosomes 1p and 19q were associated with GII/IIIs, while these changes in CDKN2A, PTEN and EGFR were more commonly associated with GBMs.<h4>Conclusions</h4>GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression.
format	article
author	Xiaowei Guan Jaime Vengoechea Siyuan Zheng Andrew E Sloan Yanwen Chen Daniel J Brat Brian Patrick O'Neill John de Groot Shlomit Yust-Katz Wai-Kwan Alfred Yung Mark L Cohen Kenneth D Aldape Steven Rosenfeld Roeland G W Verhaak Jill S Barnholtz-Sloan
author_facet	Xiaowei Guan Jaime Vengoechea Siyuan Zheng Andrew E Sloan Yanwen Chen Daniel J Brat Brian Patrick O'Neill John de Groot Shlomit Yust-Katz Wai-Kwan Alfred Yung Mark L Cohen Kenneth D Aldape Steven Rosenfeld Roeland G W Verhaak Jill S Barnholtz-Sloan
author_sort	Xiaowei Guan
title	Molecular subtypes of glioblastoma are relevant to lower grade glioma.
title_short	Molecular subtypes of glioblastoma are relevant to lower grade glioma.
title_full	Molecular subtypes of glioblastoma are relevant to lower grade glioma.
title_fullStr	Molecular subtypes of glioblastoma are relevant to lower grade glioma.
title_full_unstemmed	Molecular subtypes of glioblastoma are relevant to lower grade glioma.
title_sort	molecular subtypes of glioblastoma are relevant to lower grade glioma.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/11d06f53ffa14d86ae428b8cf35f5a14
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Molecular subtypes of glioblastoma are relevant to lower grade glioma.

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