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. 2023 Oct 20;11(1):93.
doi: 10.1186/s40364-023-00533-1.

Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients

Maria Kfoury  1   2 , Reda El Hazzaz  3 , Claire Sanson  4 , Felix Blanc Durand  5 , Judith Michels  5 , Emeline Colomba Blameble  5 , Roseline Tang  6 , Audrey Le Formal  7 , Elodie Lecerf  5 , Sebastien Gouy  8 , Amandine Maulard  8 , Patricia Pautier  5 , Etienne Rouleau  6 , Alexandra Leary  5   7
Affiliations

Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients

Maria Kfoury et al. Biomark Res. .

Abstract

Genomic testing is crucial for the management of ovarian cancer. DNA from biopsies at diagnostic laparoscopies or interval debulking surgery after neoadjuvant chemotherapy, has a high failure rate. At relapse, biopsies may not be feasible. The aim of our study was to evaluate the feasibility and usefulness of measuring genomic instability score (GIS) on cell-free DNA (cfDNA) from ascites.Patients enrolled in a prospective study (NCT03010124) consented to analysis of biological samples. CfDNA was extracted from 1 to 4 ml of double-centrifuged fresh ascites. Targeted Next-generation sequencing (NGS) including TP53 mutation (TP53m) was performed on cfDNA to confirm the presence of tumor cfDNA. Single Nucleotide Polymorphism Array estimating somatic copy number alterations (SCNA) was performed to calculate GIS for Homologous-Recombination deficiency (HRD).Twenty nine ascites were collected from 20 patients with suspected or confirmed OC. 93% (27/29) samples had detectable cfDNA (median 1120 ng [24-5732]) even when obtained during chemotherapy. A deleterious mutation was identified in 100%, with high allelic frequencies (median 60% [3.3-87%]), confirming that cfDNA was tumoral. SCNA analyses on 17 patients showed 11 high GIS, and 6 low GIS. 4 patients with confirmed BRCA mutation had a high GIS on ascites. When available from the same patient, SCNA profiles on ascites and tumor were superimposable.Ascites is frequent at diagnosis and relapse and yields large amounts of tumoral cfDNA. SCNA analysis on ascitic cfDNA is feasible and can detect the same HRD scar as tumor testing. Ascites could provide an alternative to tumor sampling for HRD and BRCA testing.

Keywords: Ascites; Circulating Tumor DNA; Genomic instability score; Homologous recombination deficiency; Ovarian cancer.

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Conflict of interest statement

The authors declare that they have no competing interests related to this study.

Figures

Fig. 1
Fig. 1
High yield of tumoral cell-free DNA in ascites Abbreviations: cfDNA: cell-free DNA
Fig. 2
Fig. 2
Comparison between SCNA profiles derived from tumor tissue and circulating tumor DNA Abbreviations: CGHa: Comparative Genomic Hybridization Array, SCNA: Somatic Copy Number Alteration, SNP: Single Nucleotide Polymorphism Array
See this image and copyright information in PMC

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