Comparison of tumor-informed and tumor-naïve sequencing assays for ctDNA detection in breast cancer
© 2023 The Authors. Published under the terms of the CC BY 4.0 license..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
EMBO molecular medicine - 15(2023), 6 vom: 07. Juni, Seite e16505 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Santonja, Angela [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Biomarkers, Tumor |
|---|
| Anmerkungen: |
Date Completed 08.06.2023 Date Revised 20.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.15252/emmm.202216505 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM35664720X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM35664720X | ||
| 003 | DE-627 | ||
| 005 | 20240320233125.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.15252/emmm.202216505 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1337.xml |
| 035 | |a (DE-627)NLM35664720X | ||
| 035 | |a (NLM)37161793 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Santonja, Angela |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Comparison of tumor-informed and tumor-naïve sequencing assays for ctDNA detection in breast cancer |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.06.2023 | ||
| 500 | |a Date Revised 20.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Published under the terms of the CC BY 4.0 license. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a circulating tumor DNA | |
| 650 | 4 | |a hybrid capture | |
| 650 | 4 | |a liquid biopsy | |
| 650 | 4 | |a multiplex PCR | |
| 650 | 4 | |a whole-genome sequencing | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a Circulating Tumor DNA |2 NLM | |
| 700 | 1 | |a Cooper, Wendy N |e verfasserin |4 aut | |
| 700 | 1 | |a Eldridge, Matthew D |e verfasserin |4 aut | |
| 700 | 1 | |a Edwards, Paul A W |e verfasserin |4 aut | |
| 700 | 1 | |a Morris, James A |e verfasserin |4 aut | |
| 700 | 1 | |a Edwards, Abigail R |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Heider, Katrin |e verfasserin |4 aut | |
| 700 | 1 | |a Couturier, Dominique-Laurent |e verfasserin |4 aut | |
| 700 | 1 | |a Vijayaraghavan, Aadhitthya |e verfasserin |4 aut | |
| 700 | 1 | |a Mennea, Paulius |e verfasserin |4 aut | |
| 700 | 1 | |a Ditter, Emma-Jane |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Christopher G |e verfasserin |4 aut | |
| 700 | 1 | |a Boursnell, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Manzano García, Raquel |e verfasserin |4 aut | |
| 700 | 1 | |a Rueda, Oscar M |e verfasserin |4 aut | |
| 700 | 1 | |a Beddowes, Emma |e verfasserin |4 aut | |
| 700 | 1 | |a Biggs, Heather |e verfasserin |4 aut | |
| 700 | 1 | |a Sammut, Stephen-John |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenfeld, Nitzan |e verfasserin |4 aut | |
| 700 | 1 | |a Caldas, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Abraham, Jean E |e verfasserin |4 aut | |
| 700 | 1 | |a Gale, Davina |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t EMBO molecular medicine |d 2009 |g 15(2023), 6 vom: 07. Juni, Seite e16505 |w (DE-627)NLM192618962 |x 1757-4684 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2023 |g number:6 |g day:07 |g month:06 |g pages:e16505 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.15252/emmm.202216505 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2023 |e 6 |b 07 |c 06 |h e16505 | ||