Journal: Nature reviews. Urology
This publication is a focused review on the role of extrachromosomal DNA (ecDNA) in urothelial carcinoma.
Key points:
- Biological role of ecDNA: ecDNA is highlighted as a major driver of genomic instability and rapid tumor evolution. In urothelial carcinoma, ecDNA frequently carries amplified oncogenes, which contributes to more aggressive disease behavior.
- Impact on chromatin and transcription: ecDNA alters 3D chromatin architecture and broadly reprograms transcription, supporting oncogenic pathways and increasing intratumoral heterogeneity.
- Mutational evolution and APOBEC3: ecDNA is linked to accelerated mutational evolution, particularly in the context of APOBEC3-associated mutagenesis, further enhancing tumor adaptability and resistance potential.
- Tumor–immune interface: ecDNA modulates the tumor–immune microenvironment, with implications for immune evasion and possibly variable responsiveness to immunotherapy.
- Detection and clinical utility:
- Non-invasive detection: ecDNA can be detected non-invasively through liquid biopsies (urine and plasma).
- Digital pathology: It can also be inferred from routine histopathology slides using digital pathology approaches.
These features position ecDNA as a promising adjunct biomarker to improve early detection, risk stratification, and dynamic monitoring of treatment response in urothelial carcinoma.
Overall, the article frames ecDNA as both a mechanistic driver of aggressive disease and a practical biomarker candidate with emerging diagnostic and prognostic relevance.