Double-stranded DNA in exosomes: a novel biomarker in cancer detection

Abstract

Exosomes, small membrane vesicles (30-100 nm) of endocytic origin secreted by most cell types, contain functional biomolecules, which can be horizontally transferred to recipient cells1. Exosomes bear a specific protein and lipid composition, and carry a select set of functional mRNAs and microRNAs2. Recently, our group has shown that c-Met shed in exosomes can promote a proangiogenic and prometastatic phenotype in bone marrow-derived progenitor cells during melanoma progression3. In previous research, retrotransposon RNA transcripts, single-stranded DNA (ssDNA), mitochondrial DNA, and oncogene amplifications (i.e., c-myc) have been detected in microvesicles4,5,6. In this report, we provide evidence that tumor-derived exosomes carry double-stranded DNA (dsDNA), as demonstrated through two different approaches, using enzymatic methods (dsDNA-specific shrimp DNase) and physical/structural studies (atomic force microscopy, AFM). Furthermore, we show that exosomal DNA (exoDNA) represents the entire genome and reflects the mutational status of parental tumor cells. We also highlight the translational value of exoDNA in tumor-derived exosomes for its potential usefulness as a circulating biomarker in the early detection of cancer and metastasis.