Characteristics and Changes of DNA in Extracellular Vesicles

Chang, Xiulin; Fang, Liaoqiong; Bai, Jin; Wang, Zhibiao

doi:10.1089/dna.2019.5005

Cited by 11 publications

(10 citation statements)

References 52 publications

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“…Low-pass WGS (LP-WGS) studies of ctDNA in breast cancer have determined that CNVs associated with metastatic progression and treatment response can be observed longitudinally throughout patient treatment [5,6]. Recent data have also indicated that cancer-related CNVs can be detected in the DNA of cancer patient-derived extracellular vesicles (EVs), which are membrane-bound vesicles released from a wide range of cells including tumour cells via exocytosis or membrane budding [7][8][9][10][11][12]. Interestingly, EVs are thought to be stable in the blood for up to 30 days, and the DNA within them is protected from nuclease degradation by the vesicle lipid membrane, suggesting that the assessment of EV DNA may be a promising alternative or complement to ctDNA for non-invasive cancer diagnosis and monitoring [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Circulating Tumour DNA and Extracellular Vesicle DNA by Low-Pass Whole-Genome Sequencing Reveals Molecular Drivers of Disease in a Breast Cancer Patient

et al. 2020

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There is increasing recognition of circulating tumour DNA (ctDNA) as a non-invasive alternative to tumour tissue for the molecular characterisation and monitoring of disease. Recent evidence suggests that cancer-associated changes can also be detected in the DNA contained within extracellular vesicles (EVs). As yet, there has been limited investigation into the relationship between EV DNA and ctDNA, and no studies have examined the EV DNA of breast cancer patients. The aim of this study was to use low-pass whole-genome sequencing to identify copy number variants (CNVs) in serial samples of both ctDNA and EV DNA from a patient with breast cancer. Of the 52 CNVs identified in tumour DNA, 36 (69%) were detected in at least one ctDNA sample and 13 (25%) in at least one EV DNA sample. The number of detectable variants in ctDNA and EV DNA increased over the natural history of the patient’s disease, which was associated with progression to cerebral metastases. This case study demonstrates that, while CNVs are detectable in patient EV DNA, ctDNA has greater sensitivity than EV DNA for serial monitoring of breast cancer.

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Section: Introductionmentioning

confidence: 99%

Comparison of Circulating Tumour DNA and Extracellular Vesicle DNA by Low-Pass Whole-Genome Sequencing Reveals Molecular Drivers of Disease in a Breast Cancer Patient

et al. 2020

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“…Of note, it has recently been shown that functional KRAS protein transfer from cell to cell is an extremely rare event [29]. To date, the mechanisms by which nucleic acids are sorted and packaged within EVs have yet to be elucidated [30]. However, a growing number of publications have shown that the EVs derived from primary tumors can be preferably loaded with specific molecules [31,32], and that the expression of such molecules or lack thereof contributes to shaping the phenotype of the recipient cell.…”

Section: Discussionmentioning

confidence: 99%

Pro-Inflammatory Microenvironment Modulates the Transfer of Mutated TP53 Mediated by Tumor Exosomes

Domenis

Cifù

Mio

et al. 2021

IJMS

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Exosomes released from tumor cells are instrumental in shaping the local tumor microenvironment to allow cancer progression. Recently, it has been shown that tumor exosomes carry large fragments of dsDNA, which may reflect the mutational status of parental cells. Although it has been described that a stressful microenvironment can influence exosomal cargo, the effects on DNA packing and its transfer into recipient cells have yet to be investigated. Here, we report that exosomes derived from SW480 (human colorectal adenocarcinoma cell line) cells can carry dsDNA fragments containing the entire coding sequence of both TP53 and KRAS genes, harboring the SW480-related TP53 c.818G > A and KRAS c.35G > T typical mutations. We also report the following: that cell stimulation with lipopolysaccharides (LPS) promotes the selective packaging of the TP53 gene, but not the KRAS gene; that exosomes secreted by SW480 cells efficiently transfer the mutated sequences into normal CCD841-CoN colon epithelial and THLE-2 hepatic cells; that this mechanism is more efficient when the cells had been previously incubated with pro-inflammatory cytokines; that the TP53 gene appears actively transcribed in both recipient cells; and that mutated mRNA levels are not influenced by cytokine treatment. Our data strongly suggest that pro-inflammatory stimulation promotes the horizontal transfer of an oncogene by exosomes, although this remains a rare event. Further studies are needed to assess the impact of the oncogenic transfer by exosomes in malignant transformation and its role in tumor progression.

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“…Nonetheless, it is clear that DNA extracted from all categories of EVs is the latest and most promising biomarker for identifying tumor presence and complexity [79,80]. The size of dsDNA found in EVs ranges from~100 bp to~20 kbp [79], which can represent the entire genome and reflect the mutational status of tumor parental cells [15,26,81]. The EV nucleic acid (EV NA) population includes DNA and RNA of mutant or wild-type, and from this population, the target biomarker EV NA is detected more efficiently [82].…”

Section: Characteristics Of Extracellular Vesicle-derived Dnamentioning

confidence: 99%

Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

Hur

Lee

2021

Cancers

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Extracellular vesicles (EVs) carry RNA, proteins, lipids, and diverse biomolecules for intercellular communication. Recent studies have reported that EVs contain double-stranded DNA (dsDNA) and oncogenic mutant DNA. The advantage of EV-derived DNA (EV DNA) over cell-free DNA (cfDNA) is the stability achieved through the encapsulation in the lipid bilayer of EVs, which protects EV DNA from degradation by external factors. The existence of DNA and its stability make EVs a useful source of biomarkers. However, fundamental research on EV DNA remains limited, and many aspects of EV DNA are poorly understood. This review examines the known characteristics of EV DNA, biogenesis of DNA-containing EVs, methylation, and next-generation sequencing (NGS) analysis using EV DNA for biomarker detection. On the basis of this knowledge, this review explores how EV DNA can be incorporated into diagnosis and prognosis in clinical settings, as well as gene transfer of EV DNA and its therapeutic potential.

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Characteristics and Changes of DNA in Extracellular Vesicles

Cited by 11 publications

References 52 publications

Comparison of Circulating Tumour DNA and Extracellular Vesicle DNA by Low-Pass Whole-Genome Sequencing Reveals Molecular Drivers of Disease in a Breast Cancer Patient

Comparison of Circulating Tumour DNA and Extracellular Vesicle DNA by Low-Pass Whole-Genome Sequencing Reveals Molecular Drivers of Disease in a Breast Cancer Patient

Pro-Inflammatory Microenvironment Modulates the Transfer of Mutated TP53 Mediated by Tumor Exosomes

Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

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