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

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

• Han MR
• Lee SH
• Park JY
• Hong H
• Ho JY
• Hur SY
• Choi YJ

• KMID: 2504459
• DOI: http://doi.org/10.4143/crt.2019.700

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.

Keyword

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

Figure

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  Fig. 1. Study design. Of 10 epithelial ovarian cancer patients, one (EOC3) underwent secondary debulking surgery. Two tissue samples and two vials of ascites were collected from each debulking surgery. ctDNA, circulating tumor DNA.

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  Fig. 2. Somatic mutations detected in ascites circulating tumor DNA (ctDNA), preoperative plasma ctDNA, and tumor DNA. Genes with somatic mutations are listed on the x-axis and samples are shown on the y-axis. Nonsynonymous mutations, frameshift indels, stop-gain mutations, and nonframeshift indels are shown in blue, red, green and orange, respectively.

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  Fig. 3. Mutational concordance between ascites circulating tumor DNA (ctDNA), preoperative plasma ctDNA, and tumor DNA. (A) Numbers of somatic mutations co-detected in ascites ctDNA, preoperative plasma ctDNA, and tumor DNA are shown in red, blue, and black, respectively. (B) Comparison of mutant allele frequencies of the shared mutations between preoperative plasma ctDNA and ascites ctDNA, tumor DNA and ascites ctDNA, and tumor DNA and preoperative ctDNA. The mutant allele frequencies (MAF) are shown on the x- and y-axes.

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  Fig. 4. Circulating tumor DNA (TP53 mutant allele frequencies [MAF]) from ascites and serial plasma samples and cancer antigen 125 (CA125) kinetics during primary/secondary debulking surgeries and chemotherapy. (A) Epithelial ovarian cancer (EOC) 3 and EOC4. (B) Correlation between TP53 MAF and CA125 in the 10 EOC patients. CA125 levels (UI/mL) are shown on the x-axis, and TP53 MAF are shown on the y-axis.

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