Zhu Huanbo, Huangfu Longtao, Chen Junbing, Ji Jiafu, Xing Xiaofang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Sci China Life Sci. 2025 Jan;68(1):144-157. doi: 10.1007/s11427-024-2710-3. Epub 2024 Sep 27.
Extrachromosomal DNA (ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity, oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.
染色体外DNA（ecDNA）是一种主要存在于肿瘤细胞中的环状DNA形式。与典型的染色体DNA不同，ecDNA是环状的、自我复制的，并携带完整或部分基因片段。尽管ecDNA在癌症中的出现仍然是一个罕见事件，但最近的研究表明，ecDNA上的致癌基因扩增在许多类型的癌症中广泛存在，这意味着ecDNA在加速肿瘤进化中起着核心作用。ecDNA还与肿瘤突变负担增加、染色体不稳定甚至肿瘤微环境重塑有关。ecDNA可能在影响肿瘤异质性、药物敏感性、致癌衰老和肿瘤免疫原性方面至关重要，导致肿瘤患者预后恶化。通过这种方式，已经进行了几项临床试验来研究ecDNA在临床治疗中的重要性。在这篇综述中，我们总结了ecDNA的生物发生、特征和当前的研究方法，讨论了ecDNA导致的肿瘤异质性在癌症中的重要作用，并强调了ecDNA在癌症治疗中的潜在作用。
