INTRODUCTION: Ovarian cancer is still the most lethal gynecological malignancy with a low five-years-overall survival rate. Except for BRCA1/2 mutations there is no predictive nor prognostic marker available indicating whether a patient is in need and eligible for personalized therapy. In a previous genome-wide array study we identified different methylation patterns in type II epithelial ovarian cancer patients with either good or poor outcome (PFS < vs. > 3 years). Using methylation-specific PCR (MSP) five marker candidates showed high prognostic value whereby the marker combination RUNX3/CaMKIINα was the most promising one [Häfner et al., 2015]. Moreover, in vitro experiments provided evidence that a transcript variant of RUNX3 can mediate Cisplatin sensitivity, further underlining the clinical relevance of this gene [Heinze et al., 2018].

METHODS: In this study we aim to validate the previous described prognostic value of the five candidates, especially of RUNX3 and CaMKIINα via MSP. Therefore, 100 fresh-frozen primary type II EOC samples from two different surgical centers were tested. Furthermore, previously analyzed samples were retested to gain insight on the marker distributions throughout the tumor and possible heterogeneity. The DNA was isolated via phenol/chloroform or QiaAmp Kit, converted to bisulfite DNA and tested via optimized MSP. All samples had similar clinical parameter (histology, FIGO grade, chemotherapy).

RESULTS AND DISCUSSION: By re-testing a subset of EOC samples previous results could been confirmed. Additionally, the methylation pattern was similar after renewed sectioning for DNA extraction pointing towards little tumor heterogeneity in the analyzed samples. Interestingly the methylation rate is not as high as expected from the initial analyses. Statistical analysis of the data is currently ongoing.


Häfner N, Steinbach D, Jansen L, Diebolder H, Dürst M, Runnebaum IB. RUNX3 and CAMK2N1 hypermethylation as prognostic marker for epithelial ovarian cancer, Int J Cancer. 2016

Heinze K, Kritsch D, Mosig AS, Dürst M, Häfner N, Runnebaum IB. Functional Analyses of RUNX3 and CaMKIINα in Ovarian Cancer Cell Lines Reveal Tumor-Suppressive Functions for CaMKIINα and Dichotomous Roles for RUNX3 Transcript Variants, Int J Mol Sci. 2018

Citation Format: Karolin Heinze, Lars Jansen, Leticia Oliveira-Ferrer, Barbara Schmalfeldt, Matthias Dürst, Ingo B Runnebaum, Norman Häfner. VALIDATION OF RUNX3 AND CAMKIINα HYPERMETHYLATION AS PROGNOSTIC MARKER FOR OVARIAN CARCINOMA [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr GMM-028.