【万象城AWC(中国)基因检测】BAF 染色质重塑剂的结构破坏顺利获得恢复侵袭性表观基因组程序损害神经母细胞瘤转移

靶向药一个月费用排序

阅读听到《Mol Cancer》在. 2022 Sep 3;21(1):175.发表了一篇题目为《BAF 染色质重塑剂的结构破坏顺利获得恢复侵袭性表观基因组程序损害神经母细胞瘤转移》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Carlos Jiménez, Roberta Antonelli, Mariona Nadal-Ribelles, Laura Devis-Jauregui, Pablo Latorre, Carme Solé, Marc Masanas, Adrià Molero-Valenzuela, Aroa Soriano, Josep Sánchez de Toledo, David Llobet-Navas, Josep Roma, Francesc Posas, Eulàlia de Nadal, Soledad Gallego, Lucas Moreno, Miguel F Segura 等完成。促进了肿瘤的正确治疗与个性化用药的开展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及正确治疗临床研究内容关键词：

癌症,染色质重塑,表观遗传学,表观基因组学,转移,成神经细胞瘤, SWI/SNF

肿瘤靶向治疗基因检测临床应用结果

背景：发育过程中的表观遗传编程对于确定细胞谱系至关重要，而这种编程的改变有助于胚胎肿瘤发育的开始。在神经母细胞瘤中，神经嵴祖细胞阻断其自然分化为交感肾上腺素能细胞的过程，导致侵袭性和转移性儿科癌症的开展。研究负责致癌表观基因组网络的表观遗传调节因子对于开发针对这些肿瘤的基于表观遗传的新疗法至关重要。哺乳动物开关/蔗糖非发酵 (mSWI/SNF) ATP 依赖性染色质重塑复合物在全基因组范围内发挥作用，将表观遗传信号转化为开放染色质状态。本研究旨在分析 mSWI/SNF 对神经母细胞瘤致癌表观基因组的贡献及其作为治疗靶点的潜力。方法：使用蛋白质组学方法在神经母细胞瘤细胞中进行 mSWI/SNF 复合物的功能表征，功能丧失实验、转录组和染色质可及性分析，以及体外和体内测定。结果：神经母细胞瘤细胞包含三种主要的 mSWI/SNF 亚型，但只有顺利获得沉默其关键结构亚基 ARID1A 和 ARID1B 来破坏 BRG1 相关因子 (BAF) 复合物，顺利获得促进细胞周期阻断来损害细胞增殖。全基因组染色质重塑和转录组分析表明，BAF 破坏导致涉及整合素、钙粘蛋白和关键间充质调节剂的广泛侵袭性相关表达程序的表观遗传抑制，从而减少对细胞外基质的粘附和随后的体外侵袭，并显着降低抑制体内神经母细胞瘤转移的起始和生长。结论：我们报告了 BAF 复合物在维持允许神经母细胞瘤侵袭和转移的表观基因组程序中的新的 ATP 酶非依赖性作用，敦促开发新的 BAF 药理学结构破坏物用于治疗开发在转移性神经母细胞瘤中。关键词：癌症；染色质重塑；表观遗传学；表观基因组学；转移;成神经细胞瘤; SWI/SNF。

肿瘤发生与反复转移国际数据库描述：

Background: Epigenetic programming during development is essential for determining cell lineages, and alterations in this programming contribute to the initiation of embryonal tumour development. In neuroblastoma, neural crest progenitors block their course of natural differentiation into sympathoadrenergic cells, leading to the development of aggressive and metastatic paediatric cancer. Research of the epigenetic regulators responsible for oncogenic epigenomic networks is crucial for developing new epigenetic-based therapies against these tumours. Mammalian switch/sucrose non-fermenting (mSWI/SNF) ATP-dependent chromatin remodelling complexes act genome-wide translating epigenetic signals into open chromatin states. The present study aimed to understand the contribution of mSWI/SNF to the oncogenic epigenomes of neuroblastoma and its potential as a therapeutic target.Methods: Functional characterisation of the mSWI/SNF complexes was performed in neuroblastoma cells using proteomic approaches, loss-of-function experiments, transcriptome and chromatin accessibility analyses, and in vitro and in vivo assays.Results: Neuroblastoma cells contain three main mSWI/SNF subtypes, but only BRG1-associated factor (BAF) complex disruption through silencing of its key structural subunits, ARID1A and ARID1B, impairs cell proliferation by promoting cell cycle blockade. Genome-wide chromatin remodelling and transcriptomic analyses revealed that BAF disruption results in the epigenetic repression of an extensive invasiveness-related expression program involving integrins, cadherins, and key mesenchymal regulators, thereby reducing adhesion to the extracellular matrix and the subsequent invasion in vitro and drastically inhibiting the initiation and growth of neuroblastoma metastasis in vivo.Conclusions: We report a novel ATPase-independent role for the BAF complex in maintaining an epigenomic program that allows neuroblastoma invasiveness and metastasis, urging for the development of new BAF pharmacological structural disruptors for therapeutic exploitation in metastatic neuroblastoma.Keywords: Cancer; Chromatin remodelling; Epigenetics; Epigenomics; Metastasis; Neuroblastoma; SWI/SNF.

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