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Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis
Breast cancer (BC) is the most prevalent cancer in women. While usually detected when localized, invasive procedures are still required for diagnosis. Herein, we developed a novel ultrasensitive pipeline to detect circulating tumor DNA (ctDNA) in a series of 75 plasma samples from localized BC patie...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820510/ https://www.ncbi.nlm.nih.gov/pubmed/36613590 http://dx.doi.org/10.3390/ijms24010146 |
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author | Jiménez-Rodríguez, Begoña Alba-Bernal, Alfonso López-López, Esperanza Quirós-Ortega, María Elena Carbajosa, Guillermo Garrido-Aranda, Alicia Álvarez, Martina Godoy-Ortiz, Ana Queipo-Ortuño, María Isabel Vicioso, Luis Díaz-Córdoba, Gema Roldán-Díaz, María Dunia Velasco-Suelto, Jesús Hernando, Cristina Bermejo, Begoña Julve-Parreño, Ana Lluch, Ana Pascual, Javier Comino-Méndez, Iñaki Alba, Emilio |
author_facet | Jiménez-Rodríguez, Begoña Alba-Bernal, Alfonso López-López, Esperanza Quirós-Ortega, María Elena Carbajosa, Guillermo Garrido-Aranda, Alicia Álvarez, Martina Godoy-Ortiz, Ana Queipo-Ortuño, María Isabel Vicioso, Luis Díaz-Córdoba, Gema Roldán-Díaz, María Dunia Velasco-Suelto, Jesús Hernando, Cristina Bermejo, Begoña Julve-Parreño, Ana Lluch, Ana Pascual, Javier Comino-Méndez, Iñaki Alba, Emilio |
author_sort | Jiménez-Rodríguez, Begoña |
collection | PubMed |
description | Breast cancer (BC) is the most prevalent cancer in women. While usually detected when localized, invasive procedures are still required for diagnosis. Herein, we developed a novel ultrasensitive pipeline to detect circulating tumor DNA (ctDNA) in a series of 75 plasma samples from localized BC patients prior to any medical intervention. We first performed a tumor-informed analysis to correlate the mutations found in tumor tissue and plasma. Disregarding the tumor data next, we developed an approach to detect tumor mutations in plasma. We observed a mutation concordance between the tumor and plasma of 29.50% with a sensitivity down to 0.03% in mutant variant allele frequency (VAF). We detected mutations in 33.78% of the samples, identifying eight patients with plasma-only mutations. Altogether, we determined a specificity of 86.36% and a positive predictive value of 88.46% for BC detection. We demonstrated an association between higher ctDNA median VAF and higher tumor grade, multiple plasma mutations with a likelihood of relapse and more frequent TP53 plasma mutations in hormone receptor-negative tumors. Overall, we have developed a unique ultra-sensitive sequencing workflow with a technology not previously employed in early BC, paving the way for its application in BC screening. |
format | Online Article Text |
id | pubmed-9820510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98205102023-01-07 Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis Jiménez-Rodríguez, Begoña Alba-Bernal, Alfonso López-López, Esperanza Quirós-Ortega, María Elena Carbajosa, Guillermo Garrido-Aranda, Alicia Álvarez, Martina Godoy-Ortiz, Ana Queipo-Ortuño, María Isabel Vicioso, Luis Díaz-Córdoba, Gema Roldán-Díaz, María Dunia Velasco-Suelto, Jesús Hernando, Cristina Bermejo, Begoña Julve-Parreño, Ana Lluch, Ana Pascual, Javier Comino-Méndez, Iñaki Alba, Emilio Int J Mol Sci Article Breast cancer (BC) is the most prevalent cancer in women. While usually detected when localized, invasive procedures are still required for diagnosis. Herein, we developed a novel ultrasensitive pipeline to detect circulating tumor DNA (ctDNA) in a series of 75 plasma samples from localized BC patients prior to any medical intervention. We first performed a tumor-informed analysis to correlate the mutations found in tumor tissue and plasma. Disregarding the tumor data next, we developed an approach to detect tumor mutations in plasma. We observed a mutation concordance between the tumor and plasma of 29.50% with a sensitivity down to 0.03% in mutant variant allele frequency (VAF). We detected mutations in 33.78% of the samples, identifying eight patients with plasma-only mutations. Altogether, we determined a specificity of 86.36% and a positive predictive value of 88.46% for BC detection. We demonstrated an association between higher ctDNA median VAF and higher tumor grade, multiple plasma mutations with a likelihood of relapse and more frequent TP53 plasma mutations in hormone receptor-negative tumors. Overall, we have developed a unique ultra-sensitive sequencing workflow with a technology not previously employed in early BC, paving the way for its application in BC screening. MDPI 2022-12-21 /pmc/articles/PMC9820510/ /pubmed/36613590 http://dx.doi.org/10.3390/ijms24010146 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jiménez-Rodríguez, Begoña Alba-Bernal, Alfonso López-López, Esperanza Quirós-Ortega, María Elena Carbajosa, Guillermo Garrido-Aranda, Alicia Álvarez, Martina Godoy-Ortiz, Ana Queipo-Ortuño, María Isabel Vicioso, Luis Díaz-Córdoba, Gema Roldán-Díaz, María Dunia Velasco-Suelto, Jesús Hernando, Cristina Bermejo, Begoña Julve-Parreño, Ana Lluch, Ana Pascual, Javier Comino-Méndez, Iñaki Alba, Emilio Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis |
title | Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis |
title_full | Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis |
title_fullStr | Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis |
title_full_unstemmed | Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis |
title_short | Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis |
title_sort | development of a novel ngs methodology for ultrasensitive circulating tumor dna detection as a tool for early-stage breast cancer diagnosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820510/ https://www.ncbi.nlm.nih.gov/pubmed/36613590 http://dx.doi.org/10.3390/ijms24010146 |
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