New progress of extrachromosomal circular DNA in the diagnosis and treatment of prostate cancer
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摘要: 前列腺癌是西方国家中老年男性高发的一种恶性肿瘤。在中国，前列腺癌的患病率和发病率逐年上升，给社会带来了沉重的医疗负担。染色体外环状DNA(extrachromosomal circular DNA，eccDNA)被认为是前列腺癌的重要驱动因素，并与患者较差的预后相关。eccDNA不仅可以作为扩增癌基因的载体，还可以充当其他染色体外DNA或染色体上基因的增强子。本文综述了不同类型eccDNA的分子特征、功能和检测方法，并重点关注eccDNA在前列腺癌发生发展、肿瘤诊断和肿瘤耐药研究中的进展。此外，还讨论了eccDNA作为前列腺癌潜在诊断生物标志物和治疗靶点的作用。Abstract: Prostate cancer is a malignancy with a high incidence among middle-aged and elderly men in Western countries. In China, the escalating incidence and prevalence over the years have imposed a significant burden on the healthcare system and society. Extrachromosomal circular DNA (eccDNA) plays a critical role in prostate cancer and is associated with poorer patient prognosis. Not only does eccDNA serve as a vehicle for amplifying oncogenes, it also can act in trans as an enhancer for genes on other eccDNA or chromosomes. In this review, we provide a concise overview of the molecular characteristics, functions, and detection methods about eccDNA of different types, with a particular focus on the advancement of eccDNA in development and progression of prostate cancer, tumor diagnosis and tumor resistance research. This article also explores the role of eccDNA as a potential diagnostic biomarker and therapeutic target in prostate cancer.
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Key words:
- prostate cancer /
- eccDNA /
- extrachromosomal DNA /
- oncogene amplification /
- tumor evolution
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表 1 eccDNA的分类
名称 大小 常见位置 特点 功能 spcDNA 100 bp~10 kb 不稳定细胞 与重复染色体序列同源 启动或增强基因组不稳定性 t-circles 738 bp整数倍 只存在于ALT细胞 由端粒重复组成的双链或单链分子 参与ALT通路 microDNA 100~400 bp 肿瘤细胞 源自GC含量和外显子密度高的区域 肿瘤液体活检产生microRNA ecDNA 1~3 Mb 肿瘤细胞 无着丝粒，无端粒含有完整基因 促进癌基因扩增和癌细胞耐药性 
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表 2 不同eccDNA检测工具的比较
方法 技术 特点 ecSeg DAPI或FISH 使用U-net组合检测eccDNA和FISH探针信号检测环状DNA断点 Circle-Map WGS 精准对齐短剪接序列(>4 nts) AmpliconArchitect WGS 利用短读数据检测eccDNA上的扩增子成本低廉 Amplicon-Reconstructor OM数据结合WGS 断点检测分辨率高 Circle-finder ATAC-seq 检测肿瘤扩增前阶段eccDNA Circle-seq 环状DNA测序 有作为肿瘤诊断生物标志物的潜力高特异性的eccDNA富集测序eccDNA的全长读数 ecc_finder 环状DNA测序 用Nanopore读数检测源于重复基因座的eccDNA eccDNA-seq 环状DNA测序 捕获几千碱基大小的eccDNA scEC&T-seq 环状DNA测序 勘测eccDNA驱动的单细胞间遗传异质性 ecTag CRISPR-Cas和Casilio 实现活细胞中的eccDNA可视化 CRISPR-CATCH CRISPR-Cas 以碱基对分辨率富集分析兆碱基大小的eccDNA可以用于表观遗传分析只能富集包含已知序列的eccDNA
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