PhD (Doctor of Philosophy)
Date of Award
Committee Chair or Co-Chairs
Ronald Baisden, Scott Champney, Bill Garside, Doug Thewke
Endometriosis is one of the most common gynecological diseases as it is thought to affect up to 15% of the female population. Characterized by the growth and proliferation of endometrial tissue outside of the uterine cavity, it is a complex condition with varying degrees of severity and can affect multiple regions of the body with symptoms ranging from a total lack of symptoms to debilitating pain and infertility. The most accepted theory of how endometriosis initiates is that of retrograde menstruation; however, approximately 90% of women with unobstructed fallopian tubes are thought to have some menstrual debris in the peritoneal cavity. Therefore, this theory does not explain in full why endometriosis occurs in some but not all women who experience retrograde bleeding.
Genetic factors are thought to play a major role in the pathogenesis of endometriosis as women with a family history are 5 to 10 times more likely to develop the disease. The goal of this study was to determine if common chromosomal aberrations in the form of additions, deletions, or regions of loss of heterozygosity that may contribute to the establishment or progression of the disease are present in a population of endometriosis patients. DNA was isolated from the peripheral blood of endometriosis patients and endometriosis tissue biopsies, and it was analyzed using oligonucleotide based array comparative genomic hybridization. The results suggest that an addition on chromosome 17p13.3 may play a role in the biological mechanisms involved in endometriosis as it was identified in 75% of the DNA samples obtained from the peripheral blood and 100% of the DNA samples obtained from the tissue biopsies. This chromosomal imbalance is of particular interest as it is located in a region that harbors the tumor suppressor gene, hypermethylated in cancer-1 (HIC-1), whose aberrant expression has been reported in multiple cancers.
Endometriosis has long been thought of as a benign disease despite its malignant characteristics, and individuals with endometriosis have been demonstrated to have an increased chance of developing ovarian cancer. This was the first study to examine the DNA from endometriosis patients using oligonucleotide based array comparative genomic hybridization to investigate genetic abnormalities in endometriosis. The findings may provide a novel target for future therapeutic options as well as indicate a link between endometriosis and cancer that has not been previously reported.
Dissertation - Open Access
Burke, Natalie, "Genetic Imbalances in Endometriosis Detected by Oligonucleotide-Array Based Comparative Genomic Hybridization" (2013). Electronic Theses and Dissertations. Paper 1129. http://dc.etsu.edu/etd/1129
Copyright by the authors.