Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis

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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Bibliographic Details
Main Authors: Begoña Jiménez-Rodríguez, Alfonso Alba-Bernal, Esperanza López-López, María Elena Quirós-Ortega, Guillermo Carbajosa, Alicia Garrido-Aranda, Martina Álvarez, Ana Godoy-Ortiz, María Isabel Queipo-Ortuño, Luis Vicioso, Gema Díaz-Córdoba, María Dunia Roldán-Díaz, Jesús Velasco-Suelto, Cristina Hernando, Begoña Bermejo, Ana Julve-Parreño, Ana Lluch, Javier Pascual, Iñaki Comino-Méndez, Emilio Alba
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:International Journal of Molecular Sciences
Subjects:
circulating tumor DNA
ultra-deep sequencing
early breast cancer
liquid biopsy
Online Access:https://www.mdpi.com/1422-0067/24/1/146
Description
Summary: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 <i>TP53</i> 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.
ISSN:1661-6596
1422-0067

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