Abstract
Abstract Introduction: Impaired DNA methylation patterns hold promise as cancer biomarkers. SOX17, a member of the SOX family of transcription factors, is conserved in many species and plays critical roles in the regulation of development and stem/precursor cell function, at least partly through repression of the canonical Wnt/beta-catenin signaling pathway. Global analysis of CpG island hypermethylation and gene expression in colorectal cancer cell lines revealed that SOX17 gene silencing is associated with DNA hypermethylation. We have already shown that this gene is hypermethylated in circulating tumor cells and circulating tumor DNA of patients with breast cancer (Chimonidou et al, Clin Chem 2011, Chimonidou et al, Clin Chem, 2013). High grade serous ovarian cancer (HGSC) is the most common histological subtype of ovarian cancer, with a worse disease prognosis and overall survival. In this study, we investigated for the first time the status of SOX17 promoter methylation in patients with high grade serous ovarian cancer. Materials and methods: HGSC tumors (FFPEs) from ovarian cancer patients belonging to an independent group (n = 78) and a training group (n = 47) were analyzed. For the evaluation of the specificity of our results, a small group of 10 corresponding normal tissues from the first ten individuals of the training group was also analyzed. Genomic DNA was isolated from all samples, and then was modified by Sodium Bisulfite (SB). All SB converted DNA samples were analyzed by a real time Methylation Specific PCR (MSP) assay, for detecting SOX17 promoter methylation. The IGROV1 ovarian cancer cell line was used as a positive control in all procedures. Results: In the training group, SOX17 promoter methylation was detected in 25/47 ovarian tumor samples (53.2%) and in 5/10 corresponding normal tissues. The same 5/10 matched pathological samples of the training group, were also found methylated for the SOX17 gene. In the independent group, SOX17 promoter methylation was observed in 61/78 tumor samples (78.2%). Conclusion: Our results indicate for the first time that SOX17 promoter methylation is a frequent event in high grade serous ovarian cancer. Further investigation is required to determine the prognostic significance of SOX17 promoter methylation status in ovarian cancer and correlate these findings with patients’ clinicopathological characteristics. Citation Format: Lydia Giannopoulou, Issam Chebouti, Kitty Pavlakis, Sabine Kasimir-Bauer, Evi S. Lianidou. SOX17 gene promoter methylation in high-grade serous epithelial ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3822. doi:10.1158/1538-7445.AM2015-3822
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