Total Exosomal DNA sequencing in Pancreatic Cancer Cell Lines

Exosome-enclosed biomaterials hold the promise of a non-invasive disease diagnosis. Among these potential biomolecules, DNA is arguably very stable, a feature that is desirable for any diagnostic biomarker. However, the idea of DNA in exosome is still contentious, and whether exosomal DNA from two given cell types carries distinct DNA signature has not yet been explored. In this study, we uncovered unique DNA signatures distinguishing established cancer-free vs. pancreatic cancer patient-derived cell lines, a pattern that is absent in genomic DNA from the parental cells or exosomal DNA from multiple other cancer cell types. Deep sequencing and bioinformatic analyses surprisingly revealed that almost all exosomal DNA originates from non-coding regions of the genome, across all ten cell lines used. Of these, 44 of the DNA fragments mapping to coding region were unique to all the cancer cells only and have biomarker-like application. Further, all cancer cell lines evaluated densely map to centromeric regions of the genome in contrast to the control cells sparsely mapping throughout the genome. Taken together, analyses point to the centromeric, non-coding regions of the genome as holding clues to the origination of most exosomal DNA content, the molecular signatures thereof and the potential use as diagnostic markers for pancreatic cancer.