Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrence
Objective: Circulating tumor DNA (ctDNA) offers a minimally-invasive alternative to study genomic changes in recurrent malignancies. With a high recurrence rate, the overall survival in high-grade serous ovarian carcinoma (HGSC) has remained low. Our objectives were to determine whether ctDNA from p...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323002000 |
| _version_ | 1797422631686766592 |
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| author | Giovanni Marchi Anna Rajavuori Mai T.N. Nguyen Kaisa Huhtinen Sinikka Oksa Sakari Hietanen Sampsa Hautaniemi Johanna Hynninen Jaana Oikkonen |
| author_facet | Giovanni Marchi Anna Rajavuori Mai T.N. Nguyen Kaisa Huhtinen Sinikka Oksa Sakari Hietanen Sampsa Hautaniemi Johanna Hynninen Jaana Oikkonen |
| author_sort | Giovanni Marchi |
| collection | DOAJ |
| description | Objective: Circulating tumor DNA (ctDNA) offers a minimally-invasive alternative to study genomic changes in recurrent malignancies. With a high recurrence rate, the overall survival in high-grade serous ovarian carcinoma (HGSC) has remained low. Our objectives were to determine whether ctDNA from plasma adequately represents HGSC, and to find mutational changes at relapse suggesting therapy options that could alter patient outcome. Methods: We collected 152 longitudinal plasma and 92 fresh tissue samples from 29 HGSC patients, sequencing and detecting mutations with a gene panel of more than 700 cancer-related genes. Tumor content was measured using TP53 VAF. We analyzed the concordance between the mutations in tissue and plasma samples and calculated correlations to patient outcomes. We also searched for novel mutations appearing at relapse. Results: The concordance rate between mutations in plasma compared to tumor tissue was 83 % at diagnosis and 90 % at relapse. CtDNA was released similarly from the tubo-ovarian tumors, intra-abdominal metastases and ascites. CtDNA release was high when CA-125 level was elevated. The TP53 VAF in ctDNA from plasma samples before the third cycle of primary chemotherapy showed a negative correlation to patient outcome. At relapse, 19 novel, pathogenic DNA mutations appeared, suggesting possible actionable alterations and biological mechanisms related to chemoresistance. Conclusion: Relapse ctDNA samples reflect tissue samples well and longitudinal sampling provides a timely source for mutational profiling. The emerging genetic mutations at recurrence propose that ctDNA accurately represents the widespread disease and provides possibilities for personalized therapy options. |
| first_indexed | 2024-03-09T07:35:08Z |
| format | Article |
| id | doaj.art-52a9beadc1c04aff9b4b8d207ecc7d5f |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-09T07:35:08Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-52a9beadc1c04aff9b4b8d207ecc7d5f2023-12-03T05:40:27ZengElsevierTranslational Oncology1936-52332024-01-0139101814Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrenceGiovanni Marchi0Anna Rajavuori1Mai T.N. Nguyen2Kaisa Huhtinen3Sinikka Oksa4Sakari Hietanen5Sampsa Hautaniemi6Johanna Hynninen7Jaana Oikkonen8Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki 00291, FinlandDepartment of Obstetrics and Gynecology, University of Turku and Turku University Hospital, 20521 Turku, FinlandResearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki 00291, FinlandResearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki 00291, FinlandSatasairaala Central Hospital, Department of Obstetrics and Gynecology, 28500 Pori, FinlandDepartment of Obstetrics and Gynecology, University of Turku and Turku University Hospital, 20521 Turku, FinlandResearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki 00291, FinlandDepartment of Obstetrics and Gynecology, University of Turku and Turku University Hospital, 20521 Turku, FinlandResearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki 00291, Finland; Corresponding author at: Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, P.O. Box 63, Helsinki FI-00014, Finland.Objective: Circulating tumor DNA (ctDNA) offers a minimally-invasive alternative to study genomic changes in recurrent malignancies. With a high recurrence rate, the overall survival in high-grade serous ovarian carcinoma (HGSC) has remained low. Our objectives were to determine whether ctDNA from plasma adequately represents HGSC, and to find mutational changes at relapse suggesting therapy options that could alter patient outcome. Methods: We collected 152 longitudinal plasma and 92 fresh tissue samples from 29 HGSC patients, sequencing and detecting mutations with a gene panel of more than 700 cancer-related genes. Tumor content was measured using TP53 VAF. We analyzed the concordance between the mutations in tissue and plasma samples and calculated correlations to patient outcomes. We also searched for novel mutations appearing at relapse. Results: The concordance rate between mutations in plasma compared to tumor tissue was 83 % at diagnosis and 90 % at relapse. CtDNA was released similarly from the tubo-ovarian tumors, intra-abdominal metastases and ascites. CtDNA release was high when CA-125 level was elevated. The TP53 VAF in ctDNA from plasma samples before the third cycle of primary chemotherapy showed a negative correlation to patient outcome. At relapse, 19 novel, pathogenic DNA mutations appeared, suggesting possible actionable alterations and biological mechanisms related to chemoresistance. Conclusion: Relapse ctDNA samples reflect tissue samples well and longitudinal sampling provides a timely source for mutational profiling. The emerging genetic mutations at recurrence propose that ctDNA accurately represents the widespread disease and provides possibilities for personalized therapy options.http://www.sciencedirect.com/science/article/pii/S1936523323002000ctDNAHigh-grade serous ovarian carcinomaLiquid biopsyTargeted sequencingDNA mutations |
| spellingShingle | Giovanni Marchi Anna Rajavuori Mai T.N. Nguyen Kaisa Huhtinen Sinikka Oksa Sakari Hietanen Sampsa Hautaniemi Johanna Hynninen Jaana Oikkonen Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrence Translational Oncology ctDNA High-grade serous ovarian carcinoma Liquid biopsy Targeted sequencing DNA mutations |
| title | Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrence |
| title_full | Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrence |
| title_fullStr | Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrence |
| title_full_unstemmed | Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrence |
| title_short | Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrence |
| title_sort | extensive mutational ctdna profiles reflect high grade serous cancer tumors and reveal emerging mutations at recurrence |
| topic | ctDNA High-grade serous ovarian carcinoma Liquid biopsy Targeted sequencing DNA mutations |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323002000 |
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