Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer

Cancer Res Treat. 2020 Jul;52(3):779-788. doi: 10.4143/crt.2019.700. Epub 2020 Feb 28.

Abstract

Purpose: The purpose of this study was to identify the clinical utility of circulating tumor DNA (ctDNA) from ascites and serial plasma samples from epithelial ovarian cancer (EOC) patients.

Materials and methods: Using targeted next-generation sequencing, we analyzed a total of 55 EOC samples including ctDNA from ascites and serial plasma and gDNA from tumor tissues. Tumor tissues and ascites were collected during debulking surgeries and plasma samples were collected before and after the surgeries. Because one EOC patient underwent secondary debulking surgery, a total of 11 tumor tissues, 33 plasma samples, and 11 ascites samples were obtained from the 10 patients.

Results: Of the 10 patients, nine (90%) contained somatic mutations in both tumor tissues and ascites ctDNA. This mutational concordance was confirmed through correlation analysis. The mutational concordance between ascites and tumor tissues was valid in recurrent/progressive ovarian cancer. TP53 was the most frequently detected gene with mutations. ctDNA from serial plasma samples identified EOC progression/recurrence at a similar time or even more rapidly than cancer antigen 125, an established serum protein tumor marker for EOC.

Conclusion: Our data suggest that ascites ctDNA can be used to identify the mutational landscape of ovarian cancer for therapeutic strategy planning.

Keywords: Ascites; Circulating tumor DNA; Next-generation sequencing; Ovarian neoplasms; Plasma.

MeSH terms

  • Adenocarcinoma, Clear Cell / genetics
  • Adenocarcinoma, Clear Cell / pathology
  • Adenocarcinoma, Clear Cell / surgery
  • Adult
  • Ascites / metabolism*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Circulating Tumor DNA / analysis
  • Circulating Tumor DNA / genetics*
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / pathology
  • Cystadenocarcinoma, Serous / surgery
  • Female
  • Follow-Up Studies
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Mutation*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / surgery
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Ovarian Neoplasms / surgery
  • Plasma / chemistry*
  • Prognosis
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA