Circular DNA has a ticket to ride chromosomes
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Article Date: 19 November 2025
Authors: Noah A. Dusseau & Eunhee Yi
Source: https://www.nature.com/articles/d41586-025-03589-1
Summary
Cancer cells often carry circular extrachromosomal DNA (ecDNA) that contains oncogenes and gene-regulatory sequences. Unlike chromosomal genes, ecDNA is only reliably passed to daughter cells if it physically tethers to chromosomes during cell division; untethered ecDNA can be lost and is unequally segregated, driving tumour heterogeneity. Sankar et al. (Nature) identify specific genetic elements that enable ecDNA to hitch a ride with chromosomes, clarifying a key mechanism behind ecDNA retention and inheritance in cancer cells.
The findings explain how some ecDNAs maintain oncogene amplification across divisions, contributing to rapid tumour evolution and treatment resistance. Identifying the sequences that promote tethering suggests possible strategies to destabilise ecDNA and reduce oncogene-driven adaptability in tumours.
Key Points
- ecDNA are circular DNA fragments common in cancer that often carry oncogenes and regulatory elements.
- Reliable inheritance of ecDNA requires tethering to chromosomes during mitosis; untethered ecDNA is prone to loss and unequal segregation.
- Sankar et al. pinpoint genetic elements that promote ecDNA retention by facilitating chromosomal tethering.
- These retention mechanisms help explain tumour heterogeneity and how cancers rapidly adapt or become therapy-resistant.
- Targeting the tethering sequences or the retention process could be a new therapeutic approach to destabilise ecDNA and curb oncogene spread.
Author note
Punchy take: this is a proper step-change. The paper moves ecDNA from an observational oddity to a mechanistic target — which matters if you care about why tumours evolve so fast or shrug off treatment. Read the details if you want the how and the possible next steps for therapy.
Why should I read this?
Because if you want to know why some cancers change and resist treatment so quickly, this explains a big part of the trick. We read the study so you don’t have to dig through the technicals — it shows the sequences that let circular DNA hitch a ride on chromosomes, and that’s central to how tumours keep dangerous genes around.
Context and relevance
Understanding ecDNA tethering ties into broader efforts to explain tumour heterogeneity and treatment failure. This work builds on prior studies of ecDNA in cancer and complements recent Nature papers on ecDNA formation and function. Clinically, the discovery points to diagnostic markers and new therapeutic angles aimed at destabilising ecDNA, potentially limiting rapid oncogene amplification and reducing adaptive resistance.