Comparison of tumor‐informed and tumor‐naïve sequencing assays for ctDNA detection in breast cancer
Abstract Analysis of circulating tumor DNA (ctDNA) to monitor cancer dynamics and detect minimal residual disease has been an area of increasing interest. Multiple methods have been proposed but few studies have compared the performance of different approaches. Here, we compare detection of ctDNA in...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-05-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202216505 |
| _version_ | 1826990698167009280 |
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| author | Angela Santonja Wendy N Cooper Matthew D Eldridge Paul A W Edwards James A Morris Abigail R Edwards Hui Zhao Katrin Heider Dominique‐Laurent Couturier Aadhitthya Vijayaraghavan Paulius Mennea Emma‐Jane Ditter Christopher G Smith Chris Boursnell Raquel Manzano García Oscar M Rueda Emma Beddowes Heather Biggs Stephen‐John Sammut Nitzan Rosenfeld Carlos Caldas Jean E Abraham Davina Gale |
| author_facet | Angela Santonja Wendy N Cooper Matthew D Eldridge Paul A W Edwards James A Morris Abigail R Edwards Hui Zhao Katrin Heider Dominique‐Laurent Couturier Aadhitthya Vijayaraghavan Paulius Mennea Emma‐Jane Ditter Christopher G Smith Chris Boursnell Raquel Manzano García Oscar M Rueda Emma Beddowes Heather Biggs Stephen‐John Sammut Nitzan Rosenfeld Carlos Caldas Jean E Abraham Davina Gale |
| author_sort | Angela Santonja |
| collection | DOAJ |
| description | Abstract Analysis of circulating tumor DNA (ctDNA) to monitor cancer dynamics and detect minimal residual disease has been an area of increasing interest. Multiple methods have been proposed but few studies have compared the performance of different approaches. Here, we compare detection of ctDNA in serial plasma samples from patients with breast cancer using different tumor‐informed and tumor‐naïve assays designed to detect structural variants (SVs), single nucleotide variants (SNVs), and/or somatic copy‐number aberrations, by multiplex PCR, hybrid capture, and different depths of whole‐genome sequencing. Our results demonstrate that the ctDNA dynamics and allele fractions (AFs) were highly concordant when analyzing the same patient samples using different assays. Tumor‐informed assays showed the highest sensitivity for detection of ctDNA at low concentrations. Hybrid capture sequencing targeting between 1,347 and 7,491 tumor‐identified mutations at high depth was the most sensitive assay, detecting ctDNA down to an AF of 0.00024% (2.4 parts per million, ppm). Multiplex PCR targeting 21–47 tumor‐identified SVs per patient detected ctDNA down to 0.00047% AF (4.7 ppm) and has potential as a clinical assay. |
| first_indexed | 2024-03-07T16:44:04Z |
| format | Article |
| id | doaj.art-2ec3b01381ac40e08e679d1a4763d28e |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T08:24:24Z |
| publishDate | 2023-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-2ec3b01381ac40e08e679d1a4763d28e2024-11-03T12:37:44ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-05-0115612010.15252/emmm.202216505Comparison of tumor‐informed and tumor‐naïve sequencing assays for ctDNA detection in breast cancerAngela Santonja0Wendy N Cooper1Matthew D Eldridge2Paul A W Edwards3James A Morris4Abigail R Edwards5Hui Zhao6Katrin Heider7Dominique‐Laurent Couturier8Aadhitthya Vijayaraghavan9Paulius Mennea10Emma‐Jane Ditter11Christopher G Smith12Chris Boursnell13Raquel Manzano García14Oscar M Rueda15Emma Beddowes16Heather Biggs17Stephen‐John Sammut18Nitzan Rosenfeld19Carlos Caldas20Jean E Abraham21Davina Gale22Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreMRC Biostatistics Unit, University of CambridgeCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreDepartment of Oncology, University of CambridgeCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCancer Research UK Cambridge Centre, Cancer Research UK Cambridge Institute, Li Ka Shing CentreCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreAbstract Analysis of circulating tumor DNA (ctDNA) to monitor cancer dynamics and detect minimal residual disease has been an area of increasing interest. Multiple methods have been proposed but few studies have compared the performance of different approaches. Here, we compare detection of ctDNA in serial plasma samples from patients with breast cancer using different tumor‐informed and tumor‐naïve assays designed to detect structural variants (SVs), single nucleotide variants (SNVs), and/or somatic copy‐number aberrations, by multiplex PCR, hybrid capture, and different depths of whole‐genome sequencing. Our results demonstrate that the ctDNA dynamics and allele fractions (AFs) were highly concordant when analyzing the same patient samples using different assays. Tumor‐informed assays showed the highest sensitivity for detection of ctDNA at low concentrations. Hybrid capture sequencing targeting between 1,347 and 7,491 tumor‐identified mutations at high depth was the most sensitive assay, detecting ctDNA down to an AF of 0.00024% (2.4 parts per million, ppm). Multiplex PCR targeting 21–47 tumor‐identified SVs per patient detected ctDNA down to 0.00047% AF (4.7 ppm) and has potential as a clinical assay.https://doi.org/10.15252/emmm.202216505circulating tumor DNAliquid biopsyhybrid capturemultiplex PCRwhole‐genome sequencing |
| spellingShingle | Angela Santonja Wendy N Cooper Matthew D Eldridge Paul A W Edwards James A Morris Abigail R Edwards Hui Zhao Katrin Heider Dominique‐Laurent Couturier Aadhitthya Vijayaraghavan Paulius Mennea Emma‐Jane Ditter Christopher G Smith Chris Boursnell Raquel Manzano García Oscar M Rueda Emma Beddowes Heather Biggs Stephen‐John Sammut Nitzan Rosenfeld Carlos Caldas Jean E Abraham Davina Gale Comparison of tumor‐informed and tumor‐naïve sequencing assays for ctDNA detection in breast cancer EMBO Molecular Medicine circulating tumor DNA liquid biopsy hybrid capture multiplex PCR whole‐genome sequencing |
| title | Comparison of tumor‐informed and tumor‐naïve sequencing assays for ctDNA detection in breast cancer |
| title_full | Comparison of tumor‐informed and tumor‐naïve sequencing assays for ctDNA detection in breast cancer |
| title_fullStr | Comparison of tumor‐informed and tumor‐naïve sequencing assays for ctDNA detection in breast cancer |
| title_full_unstemmed | Comparison of tumor‐informed and tumor‐naïve sequencing assays for ctDNA detection in breast cancer |
| title_short | Comparison of tumor‐informed and tumor‐naïve sequencing assays for ctDNA detection in breast cancer |
| title_sort | comparison of tumor informed and tumor naive sequencing assays for ctdna detection in breast cancer |
| topic | circulating tumor DNA liquid biopsy hybrid capture multiplex PCR whole‐genome sequencing |
| url | https://doi.org/10.15252/emmm.202216505 |
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