Precision genome editing for genome instability and extrachromosomal DNA (ecDNA): Mechanisms and translational opportunities

Genome instability represents a central hallmark of cancer and a powerful engine of tumour evolution, fostering genetic diversity, drug resistance, and relapse. Among the most striking features of this instability is the formation of extrachromosomal DNA (ecDNA): circular, amplified DNA elements that carry oncogenes and replicate outside the chromosomes, escaping traditional segregation rules. Recent advances in sequencing, imaging, and computational analysis have revealed that ecDNA occurs far more widely across cancer types than once believed, reshaping how we understand oncogene regulation and adaptability. Despite this progress, major questions persist regarding how ecDNAs form, propagate, and contribute to tumour heterogeneity and treatment resistance. Precision genome editing has begun to illuminate these processes, offering powerful platforms to model, manipulate, and visualise genomic instability in unprecedented ways.This Research Topic aims to unite experts across genome editing, cancer genomics, and molecular oncology to address these open questions. The overarching goal is to catalyse collaboration between researchers investigating ecDNA biology and those developing genomic engineering tools. Central aims include uncovering mechanisms governing ecDNA formation and inheritance, resolving how genome editing can be employed to characterise oncogene regulation on ecDNA, and identifying new translational avenues for targeting genome instability in cancer. Contributions may include original studies, methodological advances, reviews, and perspectives that bridge technology development with biological discovery.To gather deeper insights into the interface between genome editing, genome instability, and cancer therapeutics, we welcome submissions addressing, but not limited to, the following themes:- Genome editing tools and methodologies for studying genome instability, chromosomal rearrangements, and ecDNA dynamics- Mechanisms of ecDNA biogenesis, maintenance, and segregation - including replication stress, DNA repair dysfunction, and chromatin remodelling- Functional characterisation of ecDNA-borne oncogenes and their regulatory elements using CRISPR-based approaches- Model systems for studying ecDNA and genome instability, including engineered cell lines, organoids, xenograft models, and synthetic constructs- Tumour heterogeneity and evolution driven by ecDNA and chromosomal instability, and implications for therapy resistance- Translational and therapeutic opportunities - ecDNA-targeted strategies, synthetic lethality approaches, and intersections with immunotherapy- Computational and multi-omics approaches integrating genome editing readouts with single-cell, spatial, and long-read sequencing dataWe invite researchers from oncology, genome biology, cancer genetics, translational medicine, and bioengineering to contribute. This Research Topic seeks to become a reference point at the crossroads of genome editing and cancer genome biology, ultimately aiming to accelerate translation from molecular understanding to clinical impact. Topic editors: Yuhang Wang, Zhengyu Liang Source: https://www.frontiersin.org/research-topics/81655/precision-genome-editing-for-genome-instability-and-extrachromosomal-dna-ecdna-mechanisms-and-translational-opportunities