RT Journal Article
T1 Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis
A1 Jiménez-Rodríguez, Begoña
A1 Alba-Bernal, Alfonso
A1 López-López, Esperanza
A1 Quirós-Ortega, María Elena
A1 Carbajosa, Guillermo
A1 Garrido-Aranda, Alicia
A1 Álvarez-Pérez, Martína
A1 Godoy-Ortiz, Ana
A1 Queipo-Ortuño, María Isabel
A1 Vicioso-Recio, Luis Prudencio
A1 Díaz-Córdoba, Gema
A1 Roldán-Díaz, María Dunia
A1 Velasco-Suelto, Jesús
A1 Hernando Melia, Cristina
A1 Bermejo, Begoña
A1 Julve-Parreño, Ana
A1 Lluch, Ana
A1 Pascual, Javier
A1 Comino-Méndez, Iñaki
A1 Alba-Conejo, Emilio
K1 Cancer
AB 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.
PB IOAP-MDPI
YR 2022
FD 2022-12-21
LK https://hdl.handle.net/10630/25968
UL https://hdl.handle.net/10630/25968
LA eng
NO 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
NO Comino-Mendez’s contract is funded by the Spanish Association Against Cancer Scientific Foundation (AECC). This study was supported by the “Consejería de Salud y Familias—Junta de Andalucía” (PI-0291-2019), “Fundación Unicaja” is funding Alba-Bernal’s contract and the Andalusia-Roche Network in Precision Medical Oncology Quirós-Ortega’s contract. Carbajosa-Antona’s contract is funded by the “Ayudas María Zambrano para la atracción de talento internacional—Universidad de Málaga”. Partial funding for open access charge: Universidad de Málaga
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 3 mar 2026