Guilt by association: EcDNA as a mobile transactivator in cancer

Zhu, Yanfen; Gong, Liang; Wei, Chia‐Lin

doi:10.1016/j.trecan.2022.04.011

Cited by 8 publications

(5 citation statements)

References 78 publications

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“…Formation of ecDNA in cancer ecDNA commonly believed to originate from chromosomes [22]. The exact molecular mechanism of how ecDNA was formed remains elusive.…”

Section: Biogenesis Of Ecdna In Colorectal Cancermentioning

confidence: 99%

“…Potential and challenges of ecDNA as a diagnostic and therapeutic target for CRC Further breakthroughs in ecDNA biology require efforts in genomic technology development. Despite its prevalence, ecDNA detection is limited by the specificity, sensitivity, and resolution of current methods [22]. Live cell imaging-based methods can distinguish chromosomal and ecDNA signals, but suffer from limited throughput and also DNA sequence-dependent.…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

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Extrachromosomal circular DNA in colorectal cancer: biogenesis, function and potential as therapeutic target

et al. 2023

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Extrachromosomal circular DNA (ecDNA) has gained renewed interest since its discovery more than half a century ago, emerging as critical driver of tumor evolution. ecDNA is highly prevalent in many types of cancers, including colorectal cancer (CRC), which is one of the most deadly cancers worldwide. ecDNAs play an essential role in regulating oncogene expression, intratumor heterogeneity, and resistance to therapy independently of canonical chromosomal alterations in CRC. Furthermore, the existence of ecDNAs is attributed to the patient’s prognosis, since ecDNA-based oncogene amplification adversely affects clinical outcomes. Recent understanding of ecDNA put an extra layer of complexity in the pathogenesis of CRC. In this review, we will discuss the current understanding on mechanisms of biogenesis, and distinctive features of ecDNA in CRC. In addition, we will examine how ecDNAs mediate oncogene overexpression, gene regulation, and topological interactions with active chromatin, which facilitates genetic heterogeneity, accelerates CRC malignancy, and enhances rapid adaptation to therapy resistance. Finally, we will discuss the potential diagnostic and therapeutic implications of ecDNAs in CRC.

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“…Formation of ecDNA in cancer ecDNA commonly believed to originate from chromosomes [22]. The exact molecular mechanism of how ecDNA was formed remains elusive.…”

Section: Biogenesis Of Ecdna In Colorectal Cancermentioning

confidence: 99%

Section: Conclusion and Future Perspectivementioning

confidence: 99%

Extrachromosomal circular DNA in colorectal cancer: biogenesis, function and potential as therapeutic target

et al. 2023

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“…Previous reviews explained the roles of ecDNA in cancer progression and regulation of ecDNA ( 7 – 10 ), or focused on the functions of ecDNA in specific types of cancer, such as colorectal cancer ( 11 ) and glioblastoma ( 12 ). In this review, we discuss the molecular features, functions, mechanisms of formation, and detection methods of ecDNA, with a focus on the potential clinical implications of ecDNA in cancer.…”

Section: Introductionmentioning

confidence: 99%

Extrachromosomal DNA (ecDNA) in cancer: mechanisms, functions, and clinical implications

Dong

Chen

et al. 2023

Front. Oncol.

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Extrachromosomal DNA (ecDNA) is circular DNA that plays an important role in the development and heterogeneity of cancer. The rapid evolution of methods to detect ecDNA, including microscopic and sequencing approaches, has greatly enhanced our knowledge of the role of ecDNA in cancer development and evolution. Here, we review the molecular characteristics, functions, mechanisms of formation, and detection methods of ecDNA, with a focus on the potential clinical implications of ecDNA in cancer. Specifically, we consider the role of ecDNA in acquired drug resistance, as a diagnostic and prognostic biomarker, and as a therapeutic target in the context of cancer. As the pathological and clinical significance of ecDNA continues to be explored, it is anticipated that ecDNA will have broad applications in the diagnosis, prognosis, and treatment of patients with cancer.

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“…During cell mitosis, ecDNA is replicated but segregated asymmetrically into the two daughter cells due to the lack of recognizable centromeres, which are rapidly accumulated in cancer cells due to the growth advantage with the oncogene (Nathanson et al, 2014;Turner et al, 2017). In addition to the oncogene products, amplification of certain cancer-prone regulatory elements or cancerassociated genes on ecDNA can contribute to intra-tumoral genome heterogeneity, therapeutic resistance, and poor patient prognosis (van Leen et al, 2022;Zhao et al, 2021;Zhu et al, 2022). Meanwhile, ecDNA formation is considered a major factor that drives focal amplifications (Verhaak et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, ecDNA formation is considered a major factor that drives focal amplifications (Verhaak et al, 2019). Thus, targeting ecDNA molecules might be an attractive therapeutic strategy for ecDNA-positive cancer patients (van Leen et al, 2022;Yi et al, 2022a;Zhu et al, 2022). Despite its central role in cancer biology, relatively little is known about its prevalence, distribution, function, and clinical impact in UBC.…”

Section: Introductionmentioning

confidence: 99%

Extrachromosomal Circular DNA Orchestrates Genome Heterogeneity and Outcome in Urothelial Bladder Carcinoma

Pan

Han

et al. 2023

Preprint

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Extrachromosomal circular DNA (circulome) is a newly evolved hallmark in cancer whereas its role in shaping the cancer genome heterogeneity is yet to be sufficiently understood. Here, we comprehensively characterize and exploit the circulome-associated genome heterogeneity in 80 urothelial bladder carcinoma (UBC) patients by whole-genome/exome sequencing, Circle-Seq, long-read sequencing, and RNA-seq. Our results reveal a high load and heterogeneity of UBC circulome. Many single locus and chimeric circular DNAs originating from different chromosomes are identified, including extremely chimeric circular DNAs carrying seven oncogenes and circles from nine chromosomes. Circular DNAs contribute to increased oncogene dosage and could influence genome-wide gene expression. Increased expression of DNA repair genes (LIG3, POLQ, BRCA1, and BRCA2) promote circulome generation in UBCs. The circulome is in cis correlated with hypermutation (kataegis), copy number variation, oncogene amplification, structure variation, and poor clinical outcome. These results strongly support circulome associations with UBC genome heterogeneity, progression, and outcome.

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Guilt by association: EcDNA as a mobile transactivator in cancer

Cited by 8 publications

References 78 publications

Extrachromosomal circular DNA in colorectal cancer: biogenesis, function and potential as therapeutic target

Extrachromosomal circular DNA in colorectal cancer: biogenesis, function and potential as therapeutic target

Extrachromosomal DNA (ecDNA) in cancer: mechanisms, functions, and clinical implications

Extrachromosomal Circular DNA Orchestrates Genome Heterogeneity and Outcome in Urothelial Bladder Carcinoma

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