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<p>Extrachromosomal DNA (ecDNA) has emerged as a major driver of genomic instability and rapid tumour evolution in urothelial carcinoma. In urothelial carcinoma, ecDNA amplifies oncogenes, reshapes 3D chromatin interactions, reprogrammes transcription and modulates the tumour–immune interface. Together, these features fuel intratumour heterogeneity, accelerate APOBEC3-associated mutational evolution and contribute to aggressive disease. Advances in sequencing and imaging technologies have greatly expanded our understanding of ecDNA biology. Importantly, ecDNA can be detected through non-invasive liquid biopsies, including urine and plasma, and inferred from standard histopathology slides via digital pathology. These observations suggest that ecDNA could be a valuable adjunct biomarker, enhancing current strategies for early detection, patient stratification and dynamic monitoring of treatment response.</p>

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Extrachromosomal DNA in urothelial carcinoma: mechanisms and clinical applications

  • 期刊论文

  • 发表日期：

    2026年3月19日

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  • Conghui Li,
  • Zhiqiang Hu,
  • Weimin Zhang,
  • Yongling Ji,
  • Fubing Wang,
  • Yuchen Zeng,
  • Sanju Sinha,
  • Fengbiao Mao,
  • Chunhua Lin,
  • Wei Lv

摘要

Extrachromosomal DNA (ecDNA) has emerged as a major driver of genomic instability and rapid tumour evolution in urothelial carcinoma. In urothelial carcinoma, ecDNA amplifies oncogenes, reshapes 3D chromatin interactions, reprogrammes transcription and modulates the tumour–immune interface. Together, these features fuel intratumour heterogeneity, accelerate APOBEC3-associated mutational evolution and contribute to aggressive disease. Advances in sequencing and imaging technologies have greatly expanded our understanding of ecDNA biology. Importantly, ecDNA can be detected through non-invasive liquid biopsies, including urine and plasma, and inferred from standard histopathology slides via digital pathology. These observations suggest that ecDNA could be a valuable adjunct biomarker, enhancing current strategies for early detection, patient stratification and dynamic monitoring of treatment response.