DNA is the master code for all processes in the cell, and advances in the sequencing of this code have revealed variations among individuals. Recently, small circular pieces of DNA, called microDNA, were discovered in our tissues and are generated by “popping out” of linear DNA from chromosomes, leaving small deletions in the DNA code. These microDNAs are most likely formed due to errors in normal DNA repair processes. Cancer forms due to alterations in a cell’s DNA code, often the result of improper DNA repair as well. Therefore, it is highly likely that microDNA generation may be altered in cancer.
In this proposal, we will determine if the generation of microDNA is cancer-specific, particularly in the context of ovarian cancer, using high-throughput DNA sequencing and bioinformatic analyses. Ovarian cancer is a difficult to detect cancer due to the location of the ovaries inside a woman’s body, resulting in the diagnosis of ovarian cancer often at late stages. The discovery of ovarian cancer-specific microDNA would provide a new biomarker of ovarian cancer that could be utilized in blood-based screening assays for the early detection of ovarian cancer. Furthermore, since microDNAs have been observed in all tissues examined, these screening assays could be translated to other types of cancer as well. The feasibility of microDNA as a blood-based biomarker for ovarian cancer will be tested using an ovarian cancer mouse model. These results will be the first to characterize alterations in microDNA generation in cancer and could result in the discovery of a new cancer biomarker. Since microDNAs are a newly discovered type of DNA, little is known about how they are formed or if microDNA perform a function inside the cell. We will also perform molecular characterization studies to answer these questions.
This grant is made possible by a donation from Phil and Judy Messing, in memory of Carol S. Messing.
Laura Dillon, Ph.D. is a postdoctoral fellow in the Department of Biochemistry and Molecular Genetics at the University of Virginia in Charlottesville, VA. Dr. Dillon completed her Ph.D. in Biochemistry and Molecular Biology under the guidance of Dr. Yuh-Hwa Wang at Wake Forest University (Winston-Salem, NC) and B.S. in Biochemistry at Virginia Tech (Blacksburg, VA). Her Ph.D. thesis research focused on the mechanism of instability at chromosomal fragile sites through the study of RET/PTC rearrangements in papillary thyroid carcinoma. Her current postdoctoral research in the laboratory of Dr. Anindya Dutta focuses on examining and characterizing microDNA, a novel class of extrachromosomal circular DNA recently discovered in the Dutta lab, particularly in the context of normal versus malignant ovarian cancer cells. She hopes that these studies could lead to the discovery of a new blood-based biomarker for the early detection and prognostication of ovarian cancer.