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Poster and E-Posters
06. Ovarian cancer
418 Genome-wide methylation profiling of circulating cell-free DNA in advanced stage epithelial ovarian cancer
  1. Caroline BVan Den Berg1,
  2. Gatske MNieuwenhuyzen-De Boer1,
  3. Ingrid Boere2,
  4. Ruben G Boers3,
  5. Joachim BM Boers3,
  6. Maurice PHM Jansen2,
  7. Wilfred Van Ijcken4,
  8. Joost Gribnau3 and
  9. Heleen JVan Beekhuizen1
  1. 1Department of Gynaecologic Oncology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands
  2. 2Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands
  3. 3Department of Developmental Biology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
  4. 4Department of Cell Biology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands

Abstract

Introduction/Background Circulating DNA methylation markers in blood are promising non-invasive biomarkers in cancer. The aims of this study are to identify differentially methylated regions in cell-free DNA (cfDNA) between healthy persons and patients with advanced stage epithelial ovarian cancer (EOC) and differences in cfDNA methylation throughout the course of the disease.

Methodology Plasma-derived cfDNA was analyzed by a high-throughput genome wide DNA methylation sequencing technique: MeD-seq. A training set of therapy naïve samples of patients with advanced stage EOC (≥FIGO stage IIIB) was compared with healthy controls to define a cfDNA methylation signature. Analysis of differentially methylated regions was performed using Chi-square test with Bonferroni correction for multiple testing. A cumulative hypermethylation score was constructed and validated in a set of pre- and postoperative samples. Tumor tissue samples were correlated with cfDNA results.

Results Forty-nine patients with advanced stage EOC and ten healthy controls were included. Patients with advanced stage EOC showed a clear distinct cfDNA methylation signature from healthy controls (p-value <0.0001). Preoperative hypermethylation scores (135; interquartile range 110–163) were significantly higher than postoperative hypermethylation scores (91; interquartile range 76–101) (p-value <0.001). cfDNA methylation signature at baseline differed from tumor tissue and was closer related to DNA methylation of immune-related cells (T-lymphocytes, neutrophil granulocytes, monocytes and B-lymphocytes) than to the primary tumor.

Conclusion MeD-seq provides a promising method for genome wide methylation profiling on cfDNA. Patients with advanced stage EOC could clearly be distinguished from healthy controls and differed pre- and postoperatively. It is a remarkable finding that the cfDNA methylation signature was not correlated with tumor tissue DNA methylation, but with immune-related cells. This led to the hypothesis that advanced stage EOC, which mainly spreads in the peritoneal cavity, leads to a cfDNA methylation profile mainly based on an immune response instead of a reflection of tumor DNA methylation.

Disclosures No.

Abstract 418 Figure 1
Abstract 418 Figure 1

https://doi.org/10.1136/ijgc-2024-ESGO.641

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