The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma

McBride Matthew J.; Pulice John L.; Beird Hannah C.; Ingram Davis R.; DAvino Andrew R.; Shern Jack F.; Charville Gregory W.; Hornick Jason L.; Nakayama Robert T.; Garcia-Rivera Enrique M.; Araujo Dejka M.; Wang Wei-Lien; Tsai Jen-Wei; Yeagley Michelle; Wagner Andrew J.; Futreal P. Andrew; Khan Javed; Lazar Alexander J.; Kadoch Cigall

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The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma

机译：SS18-SSX融合癌蛋白劫持BAF复合体瞄准和功能驱动滑膜肉瘤

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摘要

Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.

机译：滑膜肉瘤（SS）是由标志性的SS18-SSX融合癌蛋白定义的，它以两种方式使BAF复合物异常：SSX增加到SS18亚单位，并伴随着BAF47亚单位组装的丢失。在这里，我们证明SS18-SSX全局劫持染色质上的BAF复合物，以激活我们使用原发肿瘤和细胞系定义的SS转录特征。具体而言，SS18-SSX将BAF复合物从增强子重新定位到广泛的多梳结构域，以对抗PRC2介导的抑制并激活二价基因。在抑制SS18-SSX后，重组BAF47可恢复增强子激活，但增殖停滞不需要重组。这些结果建立了SS18-SSX在染色质上的全局劫持机制，并定义了两个并发BAF复杂扰动的不同贡献。

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《Cancer Cell》 |2018年第6期|共21页
作者
McBride Matthew J.; Pulice John L.; Beird Hannah C.; Ingram Davis R.; DAvino Andrew R.; Shern Jack F.; Charville Gregory W.; Hornick Jason L.; Nakayama Robert T.; Garcia-Rivera Enrique M.; Araujo Dejka M.; Wang Wei-Lien; Tsai Jen-Wei; Yeagley Michelle; Wagner Andrew J.; Futreal P. Andrew; Khan Javed; Lazar Alexander J.; Kadoch Cigall;
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作者单位

Dana Farber Canc Inst Dept Pediat Oncol 450 Brookline Ave Boston MA 02215 USA;

Dana Farber Canc Inst Dept Pediat Oncol 450 Brookline Ave Boston MA 02215 USA;

Univ Texas MD Anderson Canc Ctr Dept Genom Med Houston TX 77030 USA;

Univ Texas MD Anderson Canc Ctr Dept Pathol Houston TX 77030 USA;

Dana Farber Canc Inst Dept Pediat Oncol 450 Brookline Ave Boston MA 02215 USA;

NCI Pediat Oncol Branch Ctr Canc Res NIH Bethesda MD 20892 USA;

Stanford Univ Sch Med Dept Pathol Stanford CA 94305 USA;

Harvard Med Sch Brigham &

Womens Hosp Dept Pathol Boston MA USA;

Dana Farber Canc Inst Dept Pediat Oncol 450 Brookline Ave Boston MA 02215 USA;

Dana Farber Canc Inst Dept Pediat Oncol 450 Brookline Ave Boston MA 02215 USA;

Univ Texas MD Anderson Canc Ctr Dept Sarcoma Med Oncol Houston TX 77030 USA;

Univ Texas MD Anderson Canc Ctr Dept Pathol Houston TX 77030 USA;

Univ Texas MD Anderson Canc Ctr Dept Pathol Houston TX 77030 USA;

Univ Texas MD Anderson Canc Ctr Dept Sarcoma Med Oncol Houston TX 77030 USA;

Harvard Med Sch 450 Brookline Ave Boston MA 02215 USA;

Univ Texas MD Anderson Canc Ctr Dept Genom Med Houston TX 77030 USA;

NCI Pediat Oncol Branch Ctr Canc Res NIH Bethesda MD 20892 USA;

Univ Texas MD Anderson Canc Ctr Dept Genom Med Houston TX 77030 USA;

Dana Farber Canc Inst Dept Pediat Oncol 450 Brookline Ave Boston MA 02215 USA;

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原文格式 PDF
正文语种 eng
中图分类肿瘤学;
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2. Inactivation of Mitochondrial Complex Ⅰ Induces the Expression of a Twin Cysteine Protein that Targets and Affects Cytosolic, Chloroplastidic and Mitochondrial Function [J] . Yan Wang, Wenhui Lyu, Oliver Berkowitz, 分子植物（英文版） . 2016,第005期
3. The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma [J] . McBride Matthew J., Pulice John L., Beird Hannah C., Cancer Cell . 2018,第6期

机译：SS18-SSX融合癌蛋白劫持BAF复合体瞄准和功能驱动滑膜肉瘤
4. The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma [J] . Banito Ana, Li Xiang, Laporte Aimee N., Cancer Cell . 2018,第3期

机译：SS18-SSX癌蛋白劫持kdm2b-prc1.1驱动滑膜肉瘤
5. The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma [J] . Ana Banito, Xiang Li, Aimée N. Laporte, Cancer Cell . 2018,第2期

机译：SS18-SSX癌蛋白劫持kdm2b-prc1.1驱动滑膜肉瘤
6. Richtmyer-Meshkov and Rayleigh-Taylor instabilities at ablation front of direct-drive laser fusion targets [C] . A Marocchino, S. Atzeni, A. Schiavi Conference on Plasma Physics . 2010

机译：Richtmyer-Meshkov和瑞利泰勒稳定性在直接驱动激光融合目标的消融前部
7. BAF complex in T cell development and function. [D] . Jani, Anant Rajnikant. 2009

机译：BAF复合物在T细胞的发育和功能方面。
8. The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma [O] . Matthew J. McBride, John L. Pulice, Hannah C. Beird, -1

机译：SS18-SSX融合癌蛋白劫持BAF复杂的目标和功能来驱动滑膜肉瘤。
9. The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma [O] . Matthew J. McBride, John L. Pulice, Hannah C. Beird, 2018

机译：SS18-SSX融合癌蛋白劫持BAF复合体瞄准和功能驱动滑膜肉瘤
10. Science and Technologies for Fusion Energy With Lasers and Direct- Drive Targets. [R] . Sethian, J. D., Colombant, D. G., Giuliani, J. J., 2010

机译：具有激光和直接驱动目标的聚变能源科学与技术。

The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma

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