2026-06-01T19:56:44Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/259682026-02-03T11:07:39Zcom_10630_2254col_10630_37953

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-Pérez, Martína Godoy-Ortiz, Ana Queipo-Ortuño, María Isabel Vicioso-Recio, Luis Prudencio Díaz-Córdoba, Gema Roldán-Díaz, María Dunia Velasco-Suelto, Jesús Hernando Melia, Cristina Bermejo, Begoña Julve-Parreño, Ana Lluch, Ana Pascual, Javier Comino-Méndez, Iñaki Alba-Conejo, Emilio Cancer 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. 2023-02-16T08:01:13Z 2023-02-16T08:01:13Z 2023-02-16T08:01:13Z 2022-12-21 journal article Jiménez-Rodríguez B, Alba-Bernal A, López-López E, Quirós-Ortega ME, Carbajosa G, Garrido-Aranda A, Álvarez M, Godoy-Ortiz A, Queipo-Ortuño MI, Vicioso L, Díaz-Córdoba G, Roldán-Díaz MD, Velasco-Suelto J, Hernando C, Bermejo B, Julve-Parreño A, Lluch A, Pascual J, Comino-Méndez I, Alba E. Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis. International Journal of Molecular Sciences. 2023; 24(1):146. c https://hdl.handle.net/10630/25968 https://doi.org/10.3390/ijms24010146 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional IOAP-MDPI