Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients
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 feasibilit...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Biomarker Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40364-023-00533-1 |
| _version_ | 1797451934064443392 |
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| author | Maria Kfoury Reda El Hazzaz Claire Sanson Felix Blanc Durand Judith Michels Emeline Colomba Blameble Roseline Tang Audrey Le Formal Elodie Lecerf Sebastien Gouy Amandine Maulard Patricia Pautier Etienne Rouleau Alexandra Leary |
| author_facet | Maria Kfoury Reda El Hazzaz Claire Sanson Felix Blanc Durand Judith Michels Emeline Colomba Blameble Roseline Tang Audrey Le Formal Elodie Lecerf Sebastien Gouy Amandine Maulard Patricia Pautier Etienne Rouleau Alexandra Leary |
| author_sort | Maria Kfoury |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T15:01:38Z |
| format | Article |
| id | doaj.art-0723fed9251a4a12938d6a742423f645 |
| institution | Directory Open Access Journal |
| issn | 2050-7771 |
| language | English |
| last_indexed | 2024-03-09T15:01:38Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj.art-0723fed9251a4a12938d6a742423f6452023-11-26T13:52:32ZengBMCBiomarker Research2050-77712023-10-011111410.1186/s40364-023-00533-1Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patientsMaria Kfoury0Reda El Hazzaz1Claire Sanson2Felix Blanc Durand3Judith Michels4Emeline Colomba Blameble5Roseline Tang6Audrey Le Formal7Elodie Lecerf8Sebastien Gouy9Amandine Maulard10Patricia Pautier11Etienne Rouleau12Alexandra Leary13Department of Oncology, Gustave Roussy Cancer CenterDepartment of Medical Oncology, AR-RAZI Cancer Center, FEZDepartment of Surgery, Hôpital Pitié-SalpétrièreDepartment of Oncology, Gustave Roussy Cancer CenterDepartment of Oncology, Gustave Roussy Cancer CenterDepartment of Oncology, Gustave Roussy Cancer CenterDepartment of Medical Biology and Pathology, Cancer Genetics LaboratoryInserm UMR 981, Gustave Roussy Cancer CenterDepartment of Oncology, Gustave Roussy Cancer CenterDepartment of Surgery, Gustave Roussy Cancer CenterDepartment of Surgery, Gustave Roussy Cancer CenterDepartment of Oncology, Gustave Roussy Cancer CenterDepartment of Medical Biology and Pathology, Cancer Genetics LaboratoryDepartment of Oncology, Gustave Roussy Cancer CenterAbstract 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.https://doi.org/10.1186/s40364-023-00533-1Circulating Tumor DNAOvarian cancerHomologous recombination deficiencyGenomic instability scoreAscites |
| spellingShingle | Maria Kfoury Reda El Hazzaz Claire Sanson Felix Blanc Durand Judith Michels Emeline Colomba Blameble Roseline Tang Audrey Le Formal Elodie Lecerf Sebastien Gouy Amandine Maulard Patricia Pautier Etienne Rouleau Alexandra Leary Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients Biomarker Research Circulating Tumor DNA Ovarian cancer Homologous recombination deficiency Genomic instability score Ascites |
| title | Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients |
| title_full | Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients |
| title_fullStr | Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients |
| title_full_unstemmed | Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients |
| title_short | Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients |
| title_sort | circulating tumor dna from ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients |
| topic | Circulating Tumor DNA Ovarian cancer Homologous recombination deficiency Genomic instability score Ascites |
| url | https://doi.org/10.1186/s40364-023-00533-1 |
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