Detection rate for ESR1 mutations is higher in circulating‐tumor‐cell‐derived genomic DNA than in paired plasma cell‐free DNA samples as revealed by ddPCR

Plasma cell‐free DNA (cfDNA) analysis to track estrogen receptor 1 (ESR1) mutations is highly beneficial for the identification of tumor molecular dynamics and the improvement of personalized treatments for patients with metastatic breast cancer (MBC). Plasma‐cfDNA is, up to now, the most frequent l...

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Main Authors: Stavroula Smilkou, Aliki Ntzifa, Victoria Tserpeli, Ioanna Balgkouranidou, Alkistis Papatheodoridi, Evangelia Razis, Helena Linardou, Christos Papadimitriou, Amanda Psyrri, Flora Zagouri, Stylianos Kakolyris, Evi Lianidou
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Molecular Oncology
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Online Access:https://doi.org/10.1002/1878-0261.13787
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author Stavroula Smilkou
Aliki Ntzifa
Victoria Tserpeli
Ioanna Balgkouranidou
Alkistis Papatheodoridi
Evangelia Razis
Helena Linardou
Christos Papadimitriou
Amanda Psyrri
Flora Zagouri
Stylianos Kakolyris
Evi Lianidou
author_facet Stavroula Smilkou
Aliki Ntzifa
Victoria Tserpeli
Ioanna Balgkouranidou
Alkistis Papatheodoridi
Evangelia Razis
Helena Linardou
Christos Papadimitriou
Amanda Psyrri
Flora Zagouri
Stylianos Kakolyris
Evi Lianidou
author_sort Stavroula Smilkou
collection DOAJ
description Plasma cell‐free DNA (cfDNA) analysis to track estrogen receptor 1 (ESR1) mutations is highly beneficial for the identification of tumor molecular dynamics and the improvement of personalized treatments for patients with metastatic breast cancer (MBC). Plasma‐cfDNA is, up to now, the most frequent liquid biopsy analyte used to evaluate ESR1 mutational status. Circulating tumor cell (CTC) enumeration and molecular characterization analysis provides important clinical information in patients with MBC. In this study, we investigated whether analysis of CTCs and circulating tumor DNA (ctDNA) provide similar or complementary information for the analysis of ESR1 mutations. We analyzed both plasma‐cfDNA (n = 90) and paired CTC‐derived genomic DNA (gDNA; n = 42) from 90 MBC patients for seven ESR1 mutations. Eight out of 90 (8.9%) plasma‐cfDNA samples tested using the ddPLEX Mutation Detection Assay (Bio‐Rad, Hercules, CA, USA), were found positive for one ESR1 mutation, whereas 11/42 (26.2%) CTC‐derived gDNA samples were found positive for at least one ESR1 mutation. Direct comparison of paired samples (n = 42) revealed that the ESR1 mutation rate was higher in CTC‐derived gDNA (11/42, 26.2%) than in plasma‐cfDNA (6/42, 14.3%) samples. Our results, using this highly sensitive ddPLEX assay, reveal a higher percentage of mutations in CTC‐derived gDNAs than in paired ctDNA in patients with MBC. CTC‐derived gDNA analysis should be further evaluated as an important and complementary tool to ctDNA for identifying patients with ESR1 mutations and for guiding individualized therapy.
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spelling doaj-art-83d256daf88549b38d7939857e2dec232025-08-20T02:43:43ZengWileyMolecular Oncology1574-78911878-02612025-07-011972109211910.1002/1878-0261.13787Detection rate for ESR1 mutations is higher in circulating‐tumor‐cell‐derived genomic DNA than in paired plasma cell‐free DNA samples as revealed by ddPCRStavroula Smilkou0Aliki Ntzifa1Victoria Tserpeli2Ioanna Balgkouranidou3Alkistis Papatheodoridi4Evangelia Razis5Helena Linardou6Christos Papadimitriou7Amanda Psyrri8Flora Zagouri9Stylianos Kakolyris10Evi Lianidou11Analysis of Circulating Tumor Cells Lab, Laboratory of Analytical Chemistry, Department of Chemistry University of Athens GreeceAnalysis of Circulating Tumor Cells Lab, Laboratory of Analytical Chemistry, Department of Chemistry University of Athens GreeceAnalysis of Circulating Tumor Cells Lab, Laboratory of Analytical Chemistry, Department of Chemistry University of Athens GreeceDepartment of Medical Oncology University General Hospital of Alexandroupolis GreeceDepartment of Clinical Therapeutics, School of Medicine, Alexandra Hospital National and Kapodistrian University of Athens Athens GreeceHygeia Hospital Athens GreeceOncology Unit Metropolitan Hospital Athens GreeceOncology Unit, Aretaieion University Hospital National and Kapodistrian University of Athens GreeceDepartment of Medical Oncology, Second Department of Internal Medicine, “Attikon” University General Hospital, Athens Medical School National and Kapodistrian University of Athens GreeceDepartment of Clinical Therapeutics, School of Medicine, Alexandra Hospital National and Kapodistrian University of Athens Athens GreeceDepartment of Medical Oncology University General Hospital of Alexandroupolis GreeceAnalysis of Circulating Tumor Cells Lab, Laboratory of Analytical Chemistry, Department of Chemistry University of Athens GreecePlasma cell‐free DNA (cfDNA) analysis to track estrogen receptor 1 (ESR1) mutations is highly beneficial for the identification of tumor molecular dynamics and the improvement of personalized treatments for patients with metastatic breast cancer (MBC). Plasma‐cfDNA is, up to now, the most frequent liquid biopsy analyte used to evaluate ESR1 mutational status. Circulating tumor cell (CTC) enumeration and molecular characterization analysis provides important clinical information in patients with MBC. In this study, we investigated whether analysis of CTCs and circulating tumor DNA (ctDNA) provide similar or complementary information for the analysis of ESR1 mutations. We analyzed both plasma‐cfDNA (n = 90) and paired CTC‐derived genomic DNA (gDNA; n = 42) from 90 MBC patients for seven ESR1 mutations. Eight out of 90 (8.9%) plasma‐cfDNA samples tested using the ddPLEX Mutation Detection Assay (Bio‐Rad, Hercules, CA, USA), were found positive for one ESR1 mutation, whereas 11/42 (26.2%) CTC‐derived gDNA samples were found positive for at least one ESR1 mutation. Direct comparison of paired samples (n = 42) revealed that the ESR1 mutation rate was higher in CTC‐derived gDNA (11/42, 26.2%) than in plasma‐cfDNA (6/42, 14.3%) samples. Our results, using this highly sensitive ddPLEX assay, reveal a higher percentage of mutations in CTC‐derived gDNAs than in paired ctDNA in patients with MBC. CTC‐derived gDNA analysis should be further evaluated as an important and complementary tool to ctDNA for identifying patients with ESR1 mutations and for guiding individualized therapy.https://doi.org/10.1002/1878-0261.13787breast cancercirculating tumor cellscirculating tumor DNAdroplet digital PCRESR1 mutationsliquid biopsy
spellingShingle Stavroula Smilkou
Aliki Ntzifa
Victoria Tserpeli
Ioanna Balgkouranidou
Alkistis Papatheodoridi
Evangelia Razis
Helena Linardou
Christos Papadimitriou
Amanda Psyrri
Flora Zagouri
Stylianos Kakolyris
Evi Lianidou
Detection rate for ESR1 mutations is higher in circulating‐tumor‐cell‐derived genomic DNA than in paired plasma cell‐free DNA samples as revealed by ddPCR
Molecular Oncology
breast cancer
circulating tumor cells
circulating tumor DNA
droplet digital PCR
ESR1 mutations
liquid biopsy
title Detection rate for ESR1 mutations is higher in circulating‐tumor‐cell‐derived genomic DNA than in paired plasma cell‐free DNA samples as revealed by ddPCR
title_full Detection rate for ESR1 mutations is higher in circulating‐tumor‐cell‐derived genomic DNA than in paired plasma cell‐free DNA samples as revealed by ddPCR
title_fullStr Detection rate for ESR1 mutations is higher in circulating‐tumor‐cell‐derived genomic DNA than in paired plasma cell‐free DNA samples as revealed by ddPCR
title_full_unstemmed Detection rate for ESR1 mutations is higher in circulating‐tumor‐cell‐derived genomic DNA than in paired plasma cell‐free DNA samples as revealed by ddPCR
title_short Detection rate for ESR1 mutations is higher in circulating‐tumor‐cell‐derived genomic DNA than in paired plasma cell‐free DNA samples as revealed by ddPCR
title_sort detection rate for esr1 mutations is higher in circulating tumor cell derived genomic dna than in paired plasma cell free dna samples as revealed by ddpcr
topic breast cancer
circulating tumor cells
circulating tumor DNA
droplet digital PCR
ESR1 mutations
liquid biopsy
url https://doi.org/10.1002/1878-0261.13787
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