Genome-Wide Profiling of Extracellular Vesicles Derived from B16 Melanoma Cells Reflects Dynamic Changes in Mutation Profiles of Melanoma Cells

Abstract

Background: Extracellular vesicles (EVs) are carriers of DNA derived from parental cells, presenting a promising avenue for monitoring tumor progression. This aimed to investigate the relationship between EV DNA and the parental cell genome to establish a theoretical foundation for utilizing EVs to dynamically monitor tumor progression. Methods: Utilizing a classical model of cell tumor evolution, B16 melanoma cell lines (B16-F0, B16-F1, and B16-F10) with varying metastatic potentials, we demonstrated that EVs derived from these cells harbor stable double-stranded (dsDNA) fragments ranging from 15 to 10,000 bp. DNase I enzyme digestion, SYBR Green I staining, and TapeStation system were employed for characterization. Whole genome profiling analysis revealed a high concordance between EV DNA and the mutant spectrum of parent cells, particularly regarding single nucleotide polymorphisms (SNPs). EVs contained evolutionary relevant mutation profile of melanoma cells with different metastatic potentials and had a comparable evolutionary relationship with the parent cells. Results: (1) EVs derived from B16 melanoma cells contained stable dsDNA fragments ranging from 15 to 10,000 bp. (2) EVs DNA comprehensively covered the entire genome of parent cells. (3) EVs DNA exhibited strong consistency with small fragment mutations (SNPs, Inserts/Deletions) of parent cells, with decreasing consistency as mutation length increased. (4) EVs carried mutant gene profiles associated with melanoma cell progression and had similar evolutionary relationships with parent cells. Conclusions: This study underscores the ability of EVs DNA to reflect the mutation status of parental cells and emphasizes their potential as biomarkers for monitoring tumor evolution. These findings offer a theoretical foundation for the dynamic monitoring of tumor progression using EVs DNA.