Abstract
Simple SummaryWe reviewed characterization and the role of DNAs derived from extracellular vesicles focusing on its use for identifying biomarkers. Extracellular vesicles contain double-stranded genomic DNA reflecting the mutational status and methylation profile of the parental tumor cells. Many studies demonstrated higher stability, sensitivity, and specificity of extracellular vesicle DNAs in comparison to cell-free DNAs, demonstrating a high potential for clinical application as a source for liquid biopsy. Moreover, the horizontally transfer ability of extracellular vesicle DNAs could be utilized in therapeutics.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.
Highlights
In light of recent developments in targeted therapies [1], immunotherapies [2], and precision medicine [3], the importance of liquid biopsy for detecting cancer DNA and biomarkers has become obvious [4]
Blood biopsy is the most frequently utilized diagnostic method for almost all cancers [11]; sensitivity can be increased by using specific liquid samples that are related to specific cancers [12], for example, the urine for bladder cancer [13], saliva for head and neck cancer [14], and bronchoalveolar lavage fluid (BALF) for lung cancers [15]
The first study exploring the mechanism of horizontal gene transfer (HGT) by exosomes suggests that HGT occurs in double-strand break repair through genome editing [128]. These results suggest that the extracellular vesicles (EVs)-mediated lateral transfer of DNA between eukaryotic cells may result in aneuploidy and the accumulation of genetic factors, leading to tumor formation, which is a driving force behind mammalian genome evolution
Summary
In light of recent developments in targeted therapies [1], immunotherapies [2], and precision medicine [3], the importance of liquid biopsy for detecting cancer DNA and biomarkers has become obvious [4]. The characteristics of EVs include the representation of their original host through their cargo, showing their potential as biomarkers [15,26], and through the transfer of cellular components between cells [27,28]. Depending on their origin, biogenesis, and size, EVs are categorized into exosomes, microvesicles, microparticles, and apoptotic bodies [29,30]. The term EV is more commonly used in a broader sense, as isolating one specific subcategory remains technically difficult [31]
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