华盛顿大学Chia-Lin Wei小组的研究显示，染色体外DNA与核凝聚体结合并重组染色质结构以增强致癌转录。相关论文于2025年9月18日发表在《癌细胞》杂志上。

染色体外环状DNA （ecDNA）是癌症基因组中普遍存在的致癌改变，通常与侵袭性肿瘤行为和不良患者预后相关。虽然先前的研究提出了一种基于染色质的移动增强子模型，用于ecDNA驱动的肿瘤发生，但其在不同癌症类型中的确切机制和影响尚不清楚。他们的研究利用先进的多组学分析、表观遗传编辑和三种癌症模型的成像方法，揭示了ecDNA枢纽是核凝聚物的一个组成部分，并表现出癌症类型特异性的染色质连通性。表观遗传沉默的ecDNA特异性调控模块或化学破坏核凝聚物破坏ecDNA枢纽，取代MED1共激活子结合，抑制致癌转录，并促进细胞死亡。这些发现证实了ecDNA的反式激活子功能，并强调了驱动肿瘤发生的结构机制。这种精细化的理解扩展了他们对癌基因调控的看法，并为癌症治疗的替代治疗策略开辟了潜在的途径。

附：英文原文

Title: Extrachromosomal DNA associates with nuclear condensates and reorganizes chromatin structures to enhance oncogenic transcription

Author: Aziz Taghbalout, Chia-Hao Tung, Patricia A. Clow, Harianto Tjong, Ping Wang, Chee Hong Wong, Diane D. Mao, Rahul Maurya, Meng-Fan Huang, Chew Yee Ngan, Albert H. Kim, Chia-Lin Wei

Issue&Volume: 2025-09-18

Abstract: Extrachromosomal, circular DNA (ecDNA) is a prevalent oncogenic alteration in cancer genomes, often associated with aggressive tumor behavior and poor patient outcome. While previous studies proposed a chromatin-based mobile enhancer model for ecDNA-driven oncogenesis, its precise mechanism and impact remains unclear across diverse cancer types. Our study, utilizing advanced multi-omics profiling, epigenetic editing, and imaging approaches in three cancer models, reveals that ecDNA hubs are an integrated part of nuclear condensates and exhibit cancer-type specific chromatin connectivity. Epigenetic silencing of the ecDNA-specific regulatory modules or chemically disrupting nuclear condensates breaks down ecDNA hubs, displaces MED1 co-activator binding, inhibits oncogenic transcription, and promotes cell death. These findings substantiate the trans-activator function of ecDNA and underscore a structural mechanism driving oncogenesis. This refined understanding expands our views of oncogene regulation and opens potential avenues for alternative therapeutic strategies in cancer treatment.

DOI: 10.1016/j.ccell.2025.08.008

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00365-4