Clinical Validation of a Cell-Free DNA Gene Panel
| Autor: | Enrique Dominguez Meneses, Allison MacLeay, Aymen Baig, Ryan P. Frazier, Ju Cheng, Priscilla K. Brastianos, Jochen K. Lennerz, Maciej Pacula, Krista Hu, Hayley Robinson, Jesse Lee, Julie M. Batten, Rebecca S. Heist, A. John Iafrate, Aditya Bardia, Long P. Le, Yi Cao |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Adult Male medicine.medical_specialty DNA Copy Number Variations medicine.medical_treatment Pathology and Forensic Medicine Targeted therapy Circulating Tumor DNA 03 medical and health sciences 0302 clinical medicine Internal medicine Gene panel Neoplasms medicine Biomarkers Tumor Humans In patient Genetic Testing Treatment resistance Allele In Situ Hybridization Fluorescence Aged Neoplasm Staging Aged 80 and over business.industry Disease progression Liquid Biopsy Cancer Reproducibility of Results Middle Aged medicine.disease 030104 developmental biology Cell-free fetal DNA 030220 oncology & carcinogenesis Disease Progression Molecular Medicine Female business Cell-Free Nucleic Acids |
| Zdroj: | The Journal of molecular diagnostics : JMD. 21(4) |
| ISSN: | 1943-7811 |
| Popis: | The use of liquid biopsies to identify driver mutations in patients with solid tumors holds great promise for performing targeted therapy selection, monitoring disease progression, and detecting treatment resistance mechanisms. We describe herein the development and clinical validation of a 28-gene cell-free DNA panel that targets the most common genetic alterations in solid tumors. Bioinformatic and variant filtering solutions were developed to improve test sensitivity and specificity. The panel and these tools were used to analyze commercially available controls, allowing establishment of a limit of detection allele fraction cutoff of 0.25%, with 100% (95% CI, 81.5%–100%) specificity and 89.8% (95% CI, 81.0%–94.9%) sensitivity. In addition, we analyzed a total of 163 blood samples from patients with metastatic cancer (n = 123) and demonstrated a >90% sensitivity for detecting previously identified expected mutations. Longitudinal monitoring of patients revealed a strong correlation of variant allele frequency changes and clinical outcome. Additional clinically relevant information included identification of resistance mutations in patients receiving targeted treatment and detection of complex patterns of mutational heterogeneity. Achieving lower limits of detection will require additional improvements to molecular barcoding; however, these data strongly support clinical implementation of cell-free DNA panels in advanced cancer patients. |
| Databáze: | OpenAIRE |
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