Abstract 5168: Mitochondrial 16srRNA variants and complex III expression in serous ovarian cancer
Authors: Shakeria L. Cohen, Sharifeh Mehrabi, Edward E. Partridge, Felix Aikhionbare
Journal: Cancer Research (2016)

Abstract Patients suffering from serous ovarian cancer (SOC) are typically diagnosed at later stage, drastically decreasing their five-year survival prospect. Diagnostic tools, including the measurement of elevated levels of the CA125 protein released by ovarian tumors, provide valuable information but are inherently limited in specificity in diverse populations. Hence, there remains a need for more advanced diagnostic tests to distinguish the different histopathological subclasses to improve treatment outcome. Reactive oxygen species (ROS), by products of normal energy production within the mitochondria, are among the list of compounds believed to be involved in aging and the pathogenesis of many human diseases. Moreover, elevated ROS levels may cause subtle changes in regions of the mitochondrial genome (mtDNA) inducing oxidative stress and tumor microenvironment. Consequently, the events could be used to establish potential mtDNA markers involved in the progression of SOC as an age related disease. The aim of this study is to determine mitochondrial mutational roles and protein expression level in both precancerous and malignant stages of SOC. In the current study PCR-based sequencing was used to detect mtDNA sequence variants in the 16srRNA gene, known to be highly mutated in SOC. The gene spans 1671 to 3229 bp within the mtDNA and is highly conserved. Thirty-one frozen SOC tissue samples of four histopathological subclasses [cystadenoma, n = 7; borderline, n = 8; and malignant stages III/IV, n = 8 and normal no egg, no surface epithelium as a control, n = 8] were examined. Additionally, expression of mitochondrial complex III (Coenzyme Q-cytochrome c reductase) was evaluated using western blot analysis. Forty variants were detected of which three were unreported. G1811A, an unreported variant was detected in 50% of the borderline samples. The unreported variant C2794G was detected in normal, cystadenoma, and borderline with an increasing frequency of 50%, 83% and 100% correspondingly, however did not display in the malignant samples. A3364G an unreported variant was observed in all four categories with a frequency of approximately 70% or higher. Complex III was expressed progressively in normal, borderline and malignant samples. Moreover, the expression of complex III was significantly higher in the malignant samples compared to the normal control. Results from this study could suggest that the genetic instability of 16srRNA region may play a role in ovarian tumorigenicity. Additionally the over expression of complex III in the malignant stages could serve as a target for chemotherapy of serous ovarian disease. Citation Format: Shakeria L. Cohen, Sharifeh Mehrabi, Edward E. Partridge, Felix Aikhionbare. Mitochondrial 16srRNA variants and complex III expression in serous ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5168.