Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinoma
Circulating tumor DNA (ctDNA) analysis has emerged as a promising tool for detecting and profiling longitudinal genomics changes in cancer. While copy-number alterations (CNAs) play a major role in cancers, treatment effect monitoring using copy-number profiles has received limited attention as comp...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223014282 |
| _version_ | 1797630660846813184 |
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| author | Mai T.N. Nguyen Anna Rajavuori Kaisa Huhtinen Sakari Hietanen Johanna Hynninen Jaana Oikkonen Sampsa Hautaniemi |
| author_facet | Mai T.N. Nguyen Anna Rajavuori Kaisa Huhtinen Sakari Hietanen Johanna Hynninen Jaana Oikkonen Sampsa Hautaniemi |
| author_sort | Mai T.N. Nguyen |
| collection | DOAJ |
| description | Circulating tumor DNA (ctDNA) analysis has emerged as a promising tool for detecting and profiling longitudinal genomics changes in cancer. While copy-number alterations (CNAs) play a major role in cancers, treatment effect monitoring using copy-number profiles has received limited attention as compared to mutations. A major reason for this is the insensitivity of CNA analysis for the real-life tumor-fraction ctDNA samples. We performed copy-number analysis on 152 plasma samples obtained from 29 patients with high-grade serous ovarian cancer (HGSC) using a sequencing panel targeting over 500 genes. Twenty-one patients had temporally matched tissue and plasma sample pairs, which enabled assessing concordance with tissues sequenced with the same panel or whole-genome sequencing and to evaluate sensitivity. Our approach could detect concordant CNA profiles in most plasma samples with as low as 5% tumor content and highly amplified regions in samples with ∼1% of tumor content. Longitudinal profiles showed changes in the CNA profiles in seven out of 11 patients with high tumor-content plasma samples at relapse. These changes included focal acquired or lost copy-numbers, even though most of the genome remained stable. Two patients displayed major copy-number profile changes during therapy. Our analysis revealed ctDNA-detectable subclonal selection resulting from both surgical operations and chemotherapy. Overall, longitudinal ctDNA data showed acquired and diminished CNAs at relapse when compared to pre-treatment samples. These results highlight the importance of genomic profiling during treatment as well as underline the usability of ctDNA. |
| first_indexed | 2024-03-11T11:11:20Z |
| format | Article |
| id | doaj.art-339bd5a499f841cc86d3ba969aaf9d16 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T11:11:20Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-339bd5a499f841cc86d3ba969aaf9d162023-11-12T04:38:41ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01168115630Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinomaMai T.N. Nguyen0Anna Rajavuori1Kaisa Huhtinen2Sakari Hietanen3Johanna Hynninen4Jaana Oikkonen5Sampsa Hautaniemi6Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki 00291, FinlandDepartment of Obstetrics and Gynecology, Turku University Hospital, Kiinamyllynkatu 4, Turku 20521, FinlandResearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki 00291, Finland; Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, Turku 20014, FinlandDepartment of Obstetrics and Gynecology, Turku University Hospital, Kiinamyllynkatu 4, Turku 20521, FinlandDepartment of Obstetrics and Gynecology, Turku University Hospital, Kiinamyllynkatu 4, Turku 20521, FinlandResearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki 00291, Finland; Corresponding authors.Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki 00291, Finland; Corresponding authors.Circulating tumor DNA (ctDNA) analysis has emerged as a promising tool for detecting and profiling longitudinal genomics changes in cancer. While copy-number alterations (CNAs) play a major role in cancers, treatment effect monitoring using copy-number profiles has received limited attention as compared to mutations. A major reason for this is the insensitivity of CNA analysis for the real-life tumor-fraction ctDNA samples. We performed copy-number analysis on 152 plasma samples obtained from 29 patients with high-grade serous ovarian cancer (HGSC) using a sequencing panel targeting over 500 genes. Twenty-one patients had temporally matched tissue and plasma sample pairs, which enabled assessing concordance with tissues sequenced with the same panel or whole-genome sequencing and to evaluate sensitivity. Our approach could detect concordant CNA profiles in most plasma samples with as low as 5% tumor content and highly amplified regions in samples with ∼1% of tumor content. Longitudinal profiles showed changes in the CNA profiles in seven out of 11 patients with high tumor-content plasma samples at relapse. These changes included focal acquired or lost copy-numbers, even though most of the genome remained stable. Two patients displayed major copy-number profile changes during therapy. Our analysis revealed ctDNA-detectable subclonal selection resulting from both surgical operations and chemotherapy. Overall, longitudinal ctDNA data showed acquired and diminished CNAs at relapse when compared to pre-treatment samples. These results highlight the importance of genomic profiling during treatment as well as underline the usability of ctDNA.http://www.sciencedirect.com/science/article/pii/S0753332223014282CtDNACopy-number alterationsTargeted sequencingTreatment monitoringHigh-grade serous carcinoma |
| spellingShingle | Mai T.N. Nguyen Anna Rajavuori Kaisa Huhtinen Sakari Hietanen Johanna Hynninen Jaana Oikkonen Sampsa Hautaniemi Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinoma Biomedicine & Pharmacotherapy CtDNA Copy-number alterations Targeted sequencing Treatment monitoring High-grade serous carcinoma |
| title | Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinoma |
| title_full | Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinoma |
| title_fullStr | Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinoma |
| title_full_unstemmed | Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinoma |
| title_short | Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinoma |
| title_sort | circulating tumor dna based copy number profiles enable monitoring treatment effects during therapy in high grade serous carcinoma |
| topic | CtDNA Copy-number alterations Targeted sequencing Treatment monitoring High-grade serous carcinoma |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223014282 |
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