Abstract 1771: Extrachromosomal microDNAs in normal vertebrate tissues.

Abstract MicroDNAs are small (<400 base pairs in length) single- or double-stranded extrachromosomal circular DNAs that are derived by excision from tens of thousands of sites within the mammalian genome (Science, 2012, 336:86). Thus far, microDNAs have been detected in several mouse tissues, mouse and human cell lines, and both normal and malignant cells. Here, we examine the microDNAs across eight tissue types (brain, heart, lung, liver, thymus, spleen, kidney, and skeletal muscle) from normal adult mice and in chicken cell lines. We observed microDNAs in all tissue types, originating from thousands of unique genomic loci. As was previously described, these microDNAs are small circles (100 to 400 base pairs), possess a high GC content and are enriched in genic regions. The quantity and loci-of-origin of the microDNAs are compared between tissue types to ascertain tissue-specific differences that may be correlated with amount of cell proliferation and expression of specific genes. Previously, we suggested that the release of microDNAs leaves behind microdeletions within the source genomic loci, resulting in somatically mosaic cells. Our results confirm this possibility by demonstrating that microDNAs are universally present across cell and tissue types in vertebrates. In addition, short (2-15 bp) direct repeats that usually flank the genomic loci yielding microDNAs lead us to hypothesize that homologous-recombination or microhomology-mediated-repair may be involved in microDNA generation. A survey of microDNAs in cell lines defective in many of these repair pathways is being carried out to verify this hypothesis. Citation Format: Laura Dillon, Pankaj Kumar, Yoshiyuki Shibata, Anindya Dutta. Extrachromosomal microDNAs in normal vertebrate tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1771. doi:10.1158/1538-7445.AM2013-1771