Chromatin state profiling reveals PRC2 inhibition as a therapeutic target in NRAS-mutant melanoma.

IF 2.6 Q3 ONCOLOGY Molecular and Cellular Oncology Pub Date : 2021-10-27 eCollection Date: 2021-01-01 DOI:10.1080/23723556.2021.1986350
Christopher J Terranova
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Abstract

Recently, we have generated 284 epigenomic maps in melanoma. Using chromatin state profiling we identify an association of NRAS-mutants with bivalent Histone H3 lysine 27 trimethylation (H3K27me3) and broad H3K4me3 domains. Reprogramming of bivalent H3K27me3 occurs on critical invasive-regulators and its resolution using Enhancer of Zeste Homolog 2 (EZH2) inhibition reduces invasive capacity and tumor burden in NRAS-mutant patient samples.

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染色质状态分析揭示PRC2抑制是nras突变黑色素瘤的治疗靶点。
最近,我们已经生成了284个黑色素瘤的表观基因组图谱。通过染色质状态分析,我们确定了nras突变体与二价组蛋白H3赖氨酸27三甲基化(H3K27me3)和广泛的H3K4me3结构域的关联。在nras突变患者样本中,双价H3K27me3重编程发生在关键的侵入性调节因子上,使用Zeste同源物增强子2 (Enhancer of Zeste Homolog 2, EZH2)抑制可以降低侵入能力和肿瘤负荷。
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来源期刊
Molecular and Cellular Oncology
Molecular and Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
3.20
自引率
0.00%
发文量
18
期刊介绍: For a long time, solid neoplasms have been viewed as relatively homogeneous entities composed for the most part of malignant cells. It is now clear that tumors are highly heterogeneous structures that evolve in the context of intimate interactions between cancer cells and endothelial, stromal as well as immune cells. During the past few years, experimental and clinical oncologists have witnessed several conceptual transitions of this type. Molecular and Cellular Oncology (MCO) emerges within this conceptual framework as a high-profile forum for the publication of fundamental, translational and clinical research on cancer. The scope of MCO is broad. Submissions dealing with all aspects of oncogenesis, tumor progression and response to therapy will be welcome, irrespective of whether they focus on solid or hematological neoplasms. MCO has gathered leading scientists with expertise in multiple areas of cancer research and other fields of investigation to constitute a large, interdisciplinary, Editorial Board that will ensure the quality of articles accepted for publication. MCO will publish Original Research Articles, Brief Reports, Reviews, Short Reviews, Commentaries, Author Views (auto-commentaries) and Meeting Reports dealing with all aspects of cancer research.
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