Next-Generation Cancer Biomarkers: Extracellular Vesicle DNA as a Circulating Surrogate of Tumor DNA

Abstract

Extracellular vesicles (EVs) are produced by healthy tissues and tumor cells and are released in various bodily fluids, including blood. They are limited by bilayer phospholipidic membranes, and they carry a rich content in biomolecules. Their release cleanses the cells of their waste or serves as functional local and distant cell–cell communication and molecular exchange particles. This rich and heterogeneous content has been given intense attention in cancer physiopathology because EVs support cancer control and progression. Because of their specific active cargo, they are being evaluated as carriers of liquid biopsy biomarkers. Compared to soluble circulating biomarkers, their complexity might provide rich information on tumor and metastases status. Thanks to the acquired genomic changes commonly observed in oncogenic processes, double-stranded DNA (dsDNA) in EVs might be the latest most promising biomarker of tumor presence and complexity. This review will focus on the recent knowledge on the DNA inclusion in vesicles, the technical aspects of EV-DNA detection and quantification, and the use of EV-DNA as a clinical biomarker.

CRISPR/Cas9: Principle, Applications, and Delivery through Extracellular Vesicles

“…However, there is also a sufficient overlap of the molecular patterns of exosomes and their producer cells to allow for the identification of the producer cell type by analyzing the exosomal composition. This fact is utilized for diagnosis of a multitude of diseases (“liquid biopsies”), a procedure with enormous potential and is currently rapidly increasing clinical implementation [ 72 , 73 , 74 ].…”

Exosomes in Liquid Biopsy: The Nanometric World in the Pursuit of Precision Oncology

“…Currently, the focus of translational studies is also turning to exosomal DNA assessment, with more than 200 publications being found in PubMed in 2020. Probably, one of the most specific hallmarks of cancer is DNA mutations, which can also be captured within exosomes [ 75 ]. Many recent works take advantage of existing technologies for circulating free DNA (ctDNA) detection in LB.…”

Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

“…Therefore, the presence of DNA in excreted exosomes remains controversial and will continue to be controversial until the development of a method for isolating pure exosomes or microvesicles. 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].…”

“…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].…”