Extra chromosomal DNA in different cancers: Individual genome with important biological functions

Fath, Mohsen Karami; Oryani, Mahsa Akbari; Ramezani, Arefeh; Mojarad, Fatemeh Barjoie; Khalesi, Bahman; Delazar, Sina; Anjomrooz, Mehran; Taghizadeh, Arvin; Taghizadeh, S.; Payandeh, Zahra; Pourzardosht, Navid

doi:10.1016/j.critrevonc.2021.103477

Cited by 4 publications

(5 citation statements)

References 131 publications

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“…EccDNAs can exert vital biological functions through regulated signaling pathways that influence oxidative stress, bystander effects, and tumor progression. 32 EccDNA contributes to radiation-induced bystander effects by involving stress signaling. Irradiation affects not only the cells traversed by the radiation track but also non-irradiated neighboring cells, a response described as radiation-induced bystander effects.…”

Section: Regulatory Mechanisms Of Functional Eccdnamentioning

confidence: 99%

“…EccDNAs have been determined to play key roles in the resistance of chemo- or radio-therapy; therefore, the elimination of eccDNA may benefit a better outcome together with conventional therapy. 32 , 86 , 295 – 297 A large amount of laboratory evidence has shown that tumor cells can reversibly regulate the expression levels of key proteins by altering the amount of eccDNA, conferring different cell phenotypes for drug resistance. In addition, drug resistance may also be induced by creating double-strand DNA breaks, contributing to the conversion of eccDNA to HSR.…”

Section: Potential Applications Of Eccdnamentioning

confidence: 99%

“…More importantly, the elimination of extrachromosomally amplified proto-oncogenes has triggered efficient therapeutic efficacy, functioning as a potential strategy in dealing with malignancies. 3 , 4 , 31 , 32 …”

Section: Introductionmentioning

confidence: 99%

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Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Yang

Jia

et al. 2022

Sig Transduct Target Ther

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Extrachromosomal circular DNA (eccDNA), ranging in size from tens to millions of base pairs, is independent of conventional chromosomes. Recently, eccDNAs have been considered an unanticipated major source of somatic rearrangements, contributing to genomic remodeling through chimeric circularization and reintegration of circular DNA into the linear genome. In addition, the origin of eccDNA is considered to be associated with essential chromatin-related events, including the formation of super-enhancers and DNA repair machineries. Moreover, our understanding of the properties and functions of eccDNA has continuously and greatly expanded. Emerging investigations demonstrate that eccDNAs serve as multifunctional molecules in various organisms during diversified biological processes, such as epigenetic remodeling, telomere trimming, and the regulation of canonical signaling pathways. Importantly, its special distribution potentiates eccDNA as a measurable biomarker in many diseases, especially cancers. The loss of eccDNA homeostasis facilitates tumor initiation, malignant progression, and heterogeneous evolution in many cancers. An in-depth understanding of eccDNA provides novel insights for precision cancer treatment. In this review, we summarized the discovery history of eccDNA, discussed the biogenesis, characteristics, and functions of eccDNA. Moreover, we emphasized the role of eccDNA during tumor pathogenesis and malignant evolution. Therapeutically, we summarized potential clinical applications that target aberrant eccDNA in multiple diseases.

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Section: Regulatory Mechanisms Of Functional Eccdnamentioning

confidence: 99%

Section: Potential Applications Of Eccdnamentioning

confidence: 99%

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Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Yang

Jia

et al. 2022

Sig Transduct Target Ther

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“…Numerous studies have suggested that eccDNAs are strongly associated with the oncogenesis or development and progression of tumors ( Karami Fath et al, 2021 ; Ling et al, 2021 ; Wu et al, 2022b ) and can function as a promising biomarker in diagnosing and the prognoses of these diseases. Many studies have focused on intracranial tumors, particularly glioblastoma (GBM) ( Shiras and Mondal, 2021 ).…”

Section: Eccdna In Human Diseasesmentioning

confidence: 99%

Extrachromosomal circular DNA: Current status and future prospects

Zhao

Zhang

et al. 2022

eLife

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Extrachromosomal circular DNA (eccDNA) is a double-stranded DNA molecule found in various organisms, including humans. In the past few decades, the research on eccDNA has mainly focused on cancers and their associated diseases. Advancements in modern omics technologies have reinvigorated research on eccDNA and shed light on the role of these molecules in a range of diseases and normal cell phenotypes. In this review, we first summarize the formation of eccDNA and its modes of action in eukaryotic cells. We then outline eccDNA as a disease biomarker and reveal its regulatory mechanism. We finally discuss the future prospects of eccDNA, including basic research and clinical application. Thus, with the deepening of understanding and exploration of eccDNAs, they hold great promise in future biomedical research and clinical translational application.

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“…EccDNA is isolated from the chromosomes and circularized, widely presenting in both normal and cancerous tissues of eukaryotic organisms, where it can remain in the nucleus or be free in the plasma [ 1 – 3 ]. The size of eccDNA ranges from tens to millions of base pairs, some carry only promoter or exon elements [ 4 ], while others contain complete genes [ 5 , 6 ], whose mechanism of generation and function is different and intricate [ 2 , 7 , 8 ]. EccDNA has been reported to involve in the amplification of oncogenes and the maintenance of intra-tumor genetic heterogeneity [ 2 , 9 ], and it may play an important role in tumor surveillance, early diagnosis, treatment, and prediction of cancer.…”

Section: Introductionmentioning

confidence: 99%

Distribution and characterization of extrachromosomal circular DNA in colorectal cancer

Chen

et al. 2022

Mol Biomed

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Extrachromosomal circular DNA (eccDNA) has been shown to play an important role in the amplification of tumor genes and the maintenance of intra-tumor genetic heterogeneity, although its complex functional mechanism still remains to be elucidated. As the top three common malignancies in the world, colorectal cancer (CRC) has been threatening human life and health, whose tumorigenesis and development may have elusive connection with eccDNAs. Here, we described the extensive distribution of eccDNAs in the CRC tissues using Circle-seq, which range in size from hundreds to thousands of base pairs (bp). The distribution in tumor tissues had aggregation and tendency compared with random in tumor-adjacent tissues, accompanied with smaller and more regular circle lengths. After sequencing and restoring, we found that the shedding sites of eccDNAs in CRC had similar tendency in chromosome distribution, and focused on tumor-associated genes. Meanwhile, we combined RNA sequencing to explore the correlation of eccDNA differential expression in the gene transcription and signaling pathways, confirming a connection between eccDNA and RNA somewhere. Subsequently, we validated eccDNAs in CRC cell lines and the potential consistency of the junction sites of eccDNAs in CRC tissues and cell lines. Using fragments of the cationic amino acid transporter SLC7A1 to synthesize eccDNAs, we discovered the role of eccDNAs in different regions within the gene.

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Extra chromosomal DNA in different cancers: Individual genome with important biological functions

Cited by 4 publications

References 131 publications

Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Extrachromosomal circular DNA: Current status and future prospects

Distribution and characterization of extrachromosomal circular DNA in colorectal cancer

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