Genome-wide characterization of extrachromosomal circular DNA in gastric cancer and its potential role in carcinogenesis and cancer progression

Article Biochemistry & Molecular Biology

Circular DNA in the human germline and its association with recombination

Rasmus Amund Henriksen et al.

Summary: Extrachromosomal circular DNA (eccDNA) is present in the human germline, derived from all genomic regions, and can have transient and permanent effects on germline cells.

MOLECULAR CELL (2022)

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Article Biochemistry & Molecular Biology

CircleBase: an integrated resource and analysis platform for human eccDNAs

Xiaolu Zhao et al.

Summary: CircleBase is an integrated resource and analysis platform for curating and interpreting eccDNAs in multiple cell types. It identifies putative functional eccDNAs by incorporating sequencing datasets, computational predictions, and manual annotations, and classifies them into six sections including targeting genes, epigenetic regulations, and more. The top-ranked cancer cell eccDNAs were found to be enriched in oncogenic pathways such as the Ras and PI3K-Akt signaling pathways, while eccDNAs from healthy individuals were not significantly enriched.

NUCLEIC ACIDS RESEARCH (2022)

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Review Cell Biology

Extrachromosomal Circular DNA (eccDNA): From Chaos to Function

Shanru Zuo et al.

Summary: Extrachromosomal circular DNA (eccDNA) is a type of double-stranded circular DNA derived from chromosomes, with strong heterogeneity in sequence, length, and origin, and has been identified in both normal and cancer cells. Recent technological advancements have highlighted the potential role of eccDNA in cancers by regulating oncogene expression, chromosome accessibility, genome replication, immune response, and cellular communications. However, the functional relevance of eccDNA remains to be fully elucidated.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

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Review Genetics & Heredity

Extrachromosomal circular DNA in cancer: history, current knowledge, and methods

Julie B. Noer et al.

Summary: Extrachromosomal circular DNA (eccDNA) plays important roles in cancer pathogenesis, tumor heterogeneity evolution, and therapeutic resistance. This review provides an overview of the different names, formation mechanisms, and research methods of eccDNA, as well as explores its potential clinical value.

TRENDS IN GENETICS (2022)

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Article Cell Biology

Encoding gene RAB3B exists in linear chromosomal and circular extrachromosomal DNA and contributes to cisplatin resistance of hypopharyngeal squamous cell carcinoma via inducing autophagy

Changwei Lin et al.

Summary: Our study discovered that extrachromosomal circular DNA (eccDNA) may promote cisplatin (DDP) resistance in hypopharyngeal squamous cell carcinoma (HSCC) by amplifying related functional genes and inducing autophagy. These findings provide a theoretical basis for further exploring the role of eccDNA in drug resistance in HSCC.

CELL DEATH & DISEASE (2022)

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Article Oncology

Circle-Seq reveals genomic and disease-specific hallmarks in urinary cell-free extrachromosomal circular DNAs

Wei Lv et al.

Summary: This study discovers and characterizes urinary cell-free extrachromosomal circular DNA (eccDNA), which is GC-rich and mostly less than 1000 bp in length. The eccDNAs are found on all chromosomes but enriched on certain chromosomes. Patients with advanced chronic kidney disease have significantly higher levels of eccDNA in urine. Furthermore, eccDNA with miRNA genes is highly enriched in patients with chronic kidney disease.

CLINICAL AND TRANSLATIONAL MEDICINE (2022)

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Article Genetics & Heredity

The evolutionary dynamics of extrachromosomal DNA in human cancers

Joshua T. Lange et al.

Summary: Random segregation of extrachromosomal DNA contributes to intratumoral heterogeneity and facilitates the rapid adaptation of human tumor cells to anticancer drugs. Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. Through theoretical models, unbiased image analysis, CRISPR-based ecDNA tagging with live-cell imaging and CRISPR-C, it is shown that random ecDNA inheritance results in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted treatment.

NATURE GENETICS (2022)

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Review Biochemistry & Molecular Biology

Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Ludi Yang et al.

Summary: eccDNA, as an independent circular DNA, plays a crucial role in genomic remodeling and various biological processes. Its study provides novel insights for cancer treatment and holds great potential as a biomarker for disease diagnosis.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

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Article Multidisciplinary Sciences

ecDNA hubs drive cooperative intermolecular oncogene expression

King L. Hung et al.

Summary: Extrachromosomal DNA (ecDNA) hubs are clusters of ecDNAs within the nucleus that enable intermolecular enhancer-gene interactions, promoting oncogene overexpression. The protein-tethered ecDNA hubs facilitate intermolecular transcriptional regulation, serving as units of oncogene function and potential targets for cancer therapy.

NATURE (2021)

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Article Multidisciplinary Sciences

eccDNAs are apoptotic products with high innate immunostimulatory activity

Yuangao Wang et al.

Summary: By developing a new eccDNA purification and profiling method, the study revealed close-to-random genomic origination, mechanism of biogenesis and function of eccDNAs.

NATURE (2021)

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Article Multidisciplinary Sciences

Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma

Xue-Ke Zhao et al.

Summary: Frequent focal amplifications and ecDNAs were identified in Chinese GCA patients, with associations to chromothripsis process and dietary habits. The presence of oncogene focal amplifications in GCA patients showed diverse correlations with prognosis, highlighting ERBB2 focal amplifications as a potential prognostic marker in this population.

NATURE COMMUNICATIONS (2021)

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Article Oncology

Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription

Yanfen Zhu et al.

Summary: The study reveals that extrachromosomal, circular DNA (ecDNA) is a common and oncogenic alteration in cancer genomes, impacting transcriptional programs through chromatin interactions. ecDNAs in neurosphere and prostate cancer cell cultures show widespread intra-ecDNA and genome-wide chromosomal interactions, potentially leading to high-level expression of chromosomal genes.

CANCER CELL (2021)

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Review Biochemistry & Molecular Biology

Small extrachromosomal circular DNA (eccDNA): major functions in evolution and cancer

Xiaoxuan Ling et al.

Summary: eccDNA is a type of circular DNA that is independent of chromosomes but plays important roles in monitoring, early diagnosis, treatment, and prediction of cancer. They are commonly found in both normal and cancer cells, functioning through various mechanisms in stress response, aging, carcinogenesis, and drug resistance during cancer treatment.

MOLECULAR CANCER (2021)

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Article Oncology

Extrachromosomal circular DNAs are common and functional in esophageal squamous cell carcinoma

Zhenguo Sun et al.

Summary: This study identified the presence of eccDNAs in ESCC, explored their differential expression, and revealed potential mechanisms in ESCC development. These findings provide insights into genome plasticity and the role of eccDNAs in ESCC, offering potential targets for clinical therapies.

ANNALS OF TRANSLATIONAL MEDICINE (2021)

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Article Biochemistry & Molecular Biology