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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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