Abstract B02: DNA promoter methylation of HIST1H2BB as a potential early detection biomarker to reduce ovarian cancer disparities in the United States

Abstract

Abstract Background: Ovarian cancer disproportionately affects African American women in the United States (US) at all stages of the disease, from presentation through treatment, and ultimately leads to increased mortality and decreased survival, compared to non-Hispanic White women. Till recently, epithelial ovarian cancers were thought to arise from the ovarian surface epithelial cells. However, recent studies suggest that the majority of high-grade serous carcinomas (HGSCs) arise from lesions in the fallopian tubes. DNA promoter hypermethylation of certain genes is often an early event in tumorigenesis, and it can be detected in blood and other bodily fluids, making it a feasible biomarker strategy for early detection of tumors. Purpose of study: Therefore, we sought to determine the methylation profile of HGSCs as compared to fallopian tube epithelium. Using the Infinium HumanMethylation 450 Array, that permits to quantitatively assess over 450,000 methylation sites, within and outside of CpG islands and more than 20,000 genes per sample, at single-nucleotide resolution, we have obtained the genome-wide methylation profile of HGSC and fallopian tubal epithelium. We conducted a pilot study by comparing the global methylation status in 12 HGSC tissue samples to 15 fallopian tube epithelium samples. In addition, we compared the methylation profile among long-term survivors (more than 5 years) and short-term survivors (2-3 years) of HGSCs. Results: Our results identified the HIST1H2BB promoter as the most differentially methylated region when comparing HGSC with normal fallopian tube samples. Furthermore, we also found that HIST1H2BB is differentially methylated in HGSC patients with long-term survival when compared to patients with short-term survival. Conclusions: Taken together, these results support the potential use of HIST1H2BB promoter methylation as a diagnostic and prognostic biomarker for ovarian cancer. Our findings could lead to the development of a biomarker for the diagnosis and/or prognosis of ovarian cancer. An early detection biomarker for ovarian cancer could contribute to the reduction and eventual elimination of ovarian cancer health disparities in the US. Citation Format: Blanca L. Valle, Elisabetta Kuhn, David Sidransky, Rafael Guerrero-Preston. DNA promoter methylation of HIST1H2BB as a potential early detection biomarker to reduce ovarian cancer disparities in the United States. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B02.