TABLE 1.
Results of the main clinical studies assessing the performance of EV-DNA biomarkers.
| Mutation(s) detected | Stage of tumors: localized, metastatic, all stages | Mutant DNA localization | Type of sample | Clinical relevance and potential application | References |
| Ovarian cancer | |||||
| DROSHA, LIG4, MACROD2, SATB1, RASSF6, and BIRC2 | Metastatic | Internal double-stranded exoDNA | Ascites and plasma | Treatment with genotoxic drugs resulted in increased cancer cell micronuclei and genomic DNA and other nuclear contains into exosomes | Yokoi et al., 2019 |
| Glioblastoma | |||||
| IDH1G395A | All stages (II–IV) | Internal and external | Peripheral blood and surgical tissue sample | IDH1G395 mutation is detected in exosomes, correlation with diagnostic and prognostic in all stages, DNA-containing EVs can cross the disrupted blood–brain barrier | García-Romero et al., 2017 |
| Non-small cell lung cancer | |||||
| EGFR | Advance non-small cell lung cancer | ExoDNA (internal) and ctDNA | Plasma and matched baseline plasma and tissue biopsy samples | Combining exoDNA and ctDNA increased the sensitivity for EGFR mutation detection in plasma. Useful in M0/M1a patients | Krug et al., 2018 |
| EGFR T790M | All stages and healthy controls | ExoDNA/RNA (internal) and ctDNA | Plasma | The combination of exoDNA/RNA and ctDNA for EGFR T790M has a better sensitivity and specificity than ctDNA alone | Castellanos-Rizaldos et al., 2018 |
| EGFR | All stages | ExoDNA (internal) | Plasma | Diagnostic and prognosis | Hur et al., 2019 |
| EGFR T790M | All stages | ExoDNA (internal) and ctDNA | Plasma and bronchial washing | Diagnosis and prognosis | Park et al., 2020 |
| Urothelial carcinoma of bladder | |||||
| MDM2, ERBB2, CCND1, CCNE1, CDKN2A, PTEN, RB1 | T2, T3, T4, N0, N2 | ExoDNA (internal) and ctDNA | Urine samples | Identification of somatic mutation and copy number variation using ctDNA and exoDNA in urine samples | Lee et al., 2018 |
| Prostate cancer | |||||
| P53, MLH1, PTEN | T1c, T3 | ExoDNA internal and external | Plasma | EVs contain dsgDNA fragments that could be used to detect specific mutation. EVs could be used as potential biomarkers for diagnostic and prognosis | Lázaro-Ibáñez et al., 2014 |
| AR gene amplification, AR-V7 transcript, and T878A mutation | Metastatic castration-resistant prostate cancer | ExoDNA and exoRNA internal and external | Plasma | Selective isolation of a subset of circulating exosomes enriched for tumor origin increases sensitivity and specificity for the detection of specific alterations | Foroni et al., 2020 |
| MYC, PTEN | Metastatic castration-resistant prostate cancer | Single-stranded and double-stranded DNA | Plasma | EVs contain extracellular DNA and suggest that it could be used to monitor metastatic prostate cancer | Vagner et al., 2018 |
| Melanoma | |||||
| BRAF V600E | T3, T4 | ExoDNA (internal and external) and cfDNA | Plasma | Significant improvement in BRAF V600E mutation detection combining cfDNA and EV-DNA analysis using peptide affinity assay | Zocco et al., 2020 |
| Pancreatic cancer | |||||
| KRAS | All stages | ExoDNA (internal) and ctDNA | Plasma | Higher KRAS exo-DNA MAF was associated with decreased DFS in patients with localized disease | Allenson et al., 2017 |
| KRASG12D, TP 53R273H | Resectable | ExoDNA (internal) | Plasma | ExoDNA could be an interesting tool to diagnose pancreatic malignancies | Yang et al., 2017 |
| KRAS | All stages | ExoDNA (internal) and ctDNA | Plasma | MAF > 5% is correlated with worse DFS and OS | Bernard et al., 2019 |
MAF, mutant allele frequency. ExoDNA, exosomal DNA. Exo-DNA internal, a DNAse step was carried out prior to tumor DNA detection in exosomes. DFS, disease free survival. OS, overall survival. ctDNA, circulating tumor DNA. cfDNA, cell-free DNA. EV, extracellular vesicles. gDNA, genomic DNA. dsgDNA, double-stranded genomic DNA.