Topography of transcriptionally active chromatin in glioblastoma.
Topography of transcriptionally active chromatin in glioblastoma.
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DOI：
10.1126/sciadv.abd4676
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发表时间：
2021-04
期刊：
影响因子：
13.6
通讯作者：
Koeffler HP
中科院分区：
文献类型：
--
作者：
Xu L;Chen Y;Huang Y;Sandanaraj E;Yu JS;Lin RY;Dakle P;Ke XY;Chong YK;Koh L;Mayakonda A;Nacro K;Hill J;Huang ML;Gery S;Lim SW;Huang Z;Xu Y;Chen J;Bai L;Wang S;Wakimoto H;Yeo TT;Ang BT;Müschen M;Tang C;Tan TZ;Koeffler HP
脑癌组织中活性基因调控DNA元件的分析阐明了疾病生物学和治疗靶点。基于基因表达、DNA甲基化和基因组变异的最具侵袭性的脑肿瘤胶质母细胞瘤（GBM）的分子谱分析推进了癌症研究和临床诊断。增强子结构和调控电路管理肿瘤内在的转录多样性和亚型的身份仍然是难以捉摸的。在这里，通过绘制H3 K27 ac沉积，我们分析了95个GBM活检，12个正常脑组织和38个细胞系对应物的活性调控景观。差异调节增强子和超级增强子的分析揭示了以前未被认识的肿瘤间异质性层。变体增强子位点和转录组的综合分析确定了原发性肿瘤的四种分子亚型中转录增强子和核心调控电路的拓扑结构：AC 1-间充质，AC 1-经典，AC 2-前神经和AC 3-前神经。此外，这项研究揭示了核心致癌依赖于超级增强子驱动的转录因子，长非编码RNA和GBM中的药物靶点。通过分析转录增强子，我们提供了临床相关的见解GBM的分子分类，发病机制和治疗干预。
Profiling of active gene-regulatory DNA elements in brain cancer tissues illuminates disease biology and therapeutic targets. Molecular profiling of the most aggressive brain tumor glioblastoma (GBM) on the basis of gene expression, DNA methylation, and genomic variations advances both cancer research and clinical diagnosis. The enhancer architectures and regulatory circuitries governing tumor-intrinsic transcriptional diversity and subtype identity are still elusive. Here, by mapping H3K27ac deposition, we analyze the active regulatory landscapes across 95 GBM biopsies, 12 normal brain tissues, and 38 cell line counterparts. Analyses of differentially regulated enhancers and super-enhancers uncovered previously unrecognized layers of intertumor heterogeneity. Integrative analysis of variant enhancer loci and transcriptome identified topographies of transcriptional enhancers and core regulatory circuitries in four molecular subtypes of primary tumors: AC1-mesenchymal, AC1-classical, AC2-proneural, and AC3-proneural. Moreover, this study reveals core oncogenic dependency on super-enhancer–driven transcriptional factors, long noncoding RNAs, and druggable targets in GBM. Through profiling of transcriptional enhancers, we provide clinically relevant insights into molecular classification, pathogenesis, and therapeutic intervention of GBM.
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肿瘤基因对神经元和星形胶质细胞的去分化会在小鼠中诱导神经胶质瘤。
DOI：
10.1126/science.1226929
发表时间：
2012-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Friedmann-Morvinski D;Bushong EA;Ke E;Soda Y;Marumoto T;Singer O;Ellisman MH;Verma IM
通讯作者：
Verma IM
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
11.2
作者：
Bai L;Zhou B;Yang CY;Ji J;McEachern D;Przybranowski S;Jiang H;Hu J;Xu F;Zhao Y;Liu L;Fernandez-Salas E;Xu J;Dou Y;Wen B;Sun D;Meagher J;Stuckey J;Hayes DF;Li S;Ellis MJ;Wang S
通讯作者：
Wang S
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
14.9
作者：
Huang M;Chen Y;Yang M;Guo A;Xu Y;Xu L;Koeffler HP
通讯作者：
Koeffler HP