Abstract

Circulating Circulome: A New Source of DNA For Liquid Biopsy?

Anindya Dutta, Harry F. Byrd Professor and Chair of Biochemistry and Molecular Genetics and Professor of Pathology, University of Virginia School of Medicine

Cell-free circulating linear DNA is becoming very important for liquid biopsy. We have discovered small extrachromosomal circular DNA (eccDNA), called microDNA, in the nuclei of mammalian tissues and cell lines. Cell-free microDNAs from uniquely mapping regions of the genome are detected in plasma and serum from both mice and humans.  The cell-free circulating circles are significantly longer (30%-60% >250 bases) than cell-free circulating linear DNA (~150 bases). Tumor-derived human microDNA is detected in the mouse circulation in a mouse xenograft model of human ovarian cancer. Human lung cancers contain longer microDNA than normal lung and these may be detected in the blood. Thus, circular DNA in the circulation is a previously unexplored pool of nucleic acids that could complement miRNAs and linear DNA in liquid biopsies.