Molecular subtypes of glioblastoma are relevant to lower grade glioma.
Molecular subtypes of glioblastoma are relevant to lower grade glioma.
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DOI：
10.1371/journal.pone.0091216
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Barnholtz-Sloan JS
中科院分区：
文献类型：
--
作者：
Guan X;Vengoechea J;Zheng S;Sloan AE;Chen Y;Brat DJ;O'Neill BP;de Groot J;Yust-Katz S;Yung WK;Cohen ML;Aldape KD;Rosenfeld S;Verhaak RG;Barnholtz-Sloan JS
脑胶质瘤是成人最常见的原发性恶性脑肿瘤，其组织病理学和临床病程具有很大的异质性。目的是评估已知胶质母细胞瘤（GBM）表达和甲基化亚型与II级和III级胶质瘤（即，低级别胶质瘤）。基因表达阵列，单核苷酸多态性（SNP）阵列和临床数据，获得了228 GBM和176级II/II胶质瘤（GII/III）从可获得的伦勃朗数据集。另外两个具有IDH1突变状态的数据集用作验证数据集（一个公开可用的数据集和一个来自MD安德森的新生成的数据集）。进行无监督聚类，并与使用Verhaak等840-基因分类器分配的基因表达亚型进行比较。神经胶质瘤-CpG岛甲基化表型（G-CIMP）使用Fine等人的预测模型进行分配。基因表达的无监督聚类与Verhaak 840基因亚型组分配一致。GII/IIIs优先分配给IDH1突变和G-CIMP的前神经亚型。GBM在四种亚型中分布均匀。原神经、IDH1突变、G-CIMP GII/III的生存率明显高于其他分子亚型。只有6%的GBM是前神经性的，并且具有IDH1突变或G-CIMP，但这些肿瘤的生存率明显高于其他GBM。染色体1p和19q的拷贝数变化与GII/III相关，而CDKN2A、PTEN和EGFR的这些变化更常见于GBM。GBM基因表达和基于甲基化的亚型与GII/III相关，并与总体生存差异相关。更好地了解这些亚型和GII/III之间的关联可以进一步了解胶质瘤进展的预后和机制。
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). 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. 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. 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.
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影响因子：
64.8
作者：
Lu, Chao;Ward, Patrick S.;Kapoor, Gurpreet S.;Rohle, Dan;Turcan, Sevin;Abdel-Wahab, Omar;Edwards, Christopher R.;Khanin, Raya;Figueroa, Maria E.;Melnick, Ari;Wellen, Kathryn E.;O'Rourke, Donald M.;Berger, Shelley L.;Chan, Timothy A.;Levine, Ross L.;Mellinghoff, Ingo K.;Thompson, Craig B.
通讯作者：
Thompson, Craig B.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
50.3
作者：
Phillips, HS;Kharbanda, S;Aldape, K
通讯作者：
Aldape, K