Epigenomic landscape and 3D genome structure in pediatric high-grade glioma.
Epigenomic landscape and 3D genome structure in pediatric high-grade glioma.
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儿科高级别胶质瘤的表观基因组景观和3D基因组结构
DOI：
10.1126/sciadv.abg4126
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发表时间：
2021-06
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
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作者：
在儿童高级别胶质瘤中发现了独特的基因组结构变异，影响肿瘤基因表达。小儿高级别胶质瘤（pHGG），包括多形性胶质母细胞瘤（GBM）和弥漫性内在脑桥胶质瘤（DIPG），是病态的脑肿瘤。即使接受治疗，存活率也很低，使pHGG成为儿童癌症死亡的头号原因。高达80%的DIPG在编码组蛋白H3的基因中存在体细胞错义突变。为了研究H3 K27 M是否与改变转录调控的不同染色质结构相关，我们生成了pHGG细胞系和肿瘤组织的第一个高分辨率Hi-C图谱。通过整合来自H3 K27 M和野生型标本的转录组（RNA-seq）、增强子景观（ChIP-seq）、基因组结构（Hi-C）和染色质可及性（ATAC-seq）数据集，我们确定了已知癌基因的肿瘤特异性增强子和调控网络。我们确定了导致潜在增强子劫持和基因共扩增的基因组结构变异，包括A2 M，JAG 2和FLRT 1。总之，我们的研究结果表明三维基因组改变可能在pHGG表观遗传景观中发挥关键作用，并有助于肿瘤发生。
Distinct genomic structural variations are found in pediatric high-grade glioma, affecting tumor gene expression. Pediatric high-grade gliomas (pHGGs), including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG), are morbid brain tumors. Even with treatment survival is poor, making pHGG the number one cause of cancer death in children. Up to 80% of DIPGs harbor a somatic missense mutation in genes encoding histone H3. To investigate whether H3K27M is associated with distinct chromatin structure that alters transcription regulation, we generated the first high-resolution Hi-C maps of pHGG cell lines and tumor tissue. By integrating transcriptome (RNA-seq), enhancer landscape (ChIP-seq), genome structure (Hi-C), and chromatin accessibility (ATAC-seq) datasets from H3K27M and wild-type specimens, we identified tumor-specific enhancers and regulatory networks for known oncogenes. We identified genomic structural variations that lead to potential enhancer hijacking and gene coamplification, including A2M, JAG2, and FLRT1. Together, our results imply three-dimensional genome alterations may play a critical role in the pHGG epigenetic landscape and contribute to tumorigenesis.
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DOI：
10.1158/1078-0432.ccr-12-3066
发表时间：
2013-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cheng Z;Gong Y;Ma Y;Lu K;Lu X;Pierce LA;Thompson RC;Muller S;Knapp S;Wang J
通讯作者：
Wang J
影响因子：
16.6
作者：
Morgan SL;Mariano NC;Bermudez A;Arruda NL;Wu F;Luo Y;Shankar G;Jia L;Chen H;Hu JF;Hoffman AR;Huang CC;Pitteri SJ;Wang KC
通讯作者：
Wang KC
影响因子：
3.3
作者：
Asby DJ;Killick-Cole CL;Boulter LJ;Singleton WG;Asby CA;Wyatt MJ;Barua NU;Bienemann AS;Gill SS
通讯作者：
Gill SS
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：
16.6
作者：
Labreche, Karim;Simeonova, Iva;Kamoun, Aurelie;Gleize, Vincent;Chubb, Daniel;Letouze, Eric;Riazalhosseini, Yasser;Dobbins, Sara E.;Elarouci, Nabila;Ducray, Francois;de Reynies, Aurelien;Zelenika, Diana;Wardell, Christopher P.;Frampton, Mathew;Saulnier, Olivier;Pastinen, Tomi;Hallout, Sabrina;Figarella-Branger, Dominique;Dehais, Caroline;Idbaih, Ahmed;Mokhtari, Karima;Delattre, Jean-Yves;Huillard, Emmanuelle;Lathrop, G. Mark;Sanson, Marc;Houlston, Richard S.
通讯作者：
Houlston, Richard S.