Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA

Abstract Liquid biopsy is a valuable precision oncology tool that is increasingly used as a non-invasive approach to identify biomarkers, detect resistance mutations, monitor disease burden, and identify early recurrence. The Tempus xF liquid biopsy assay is a 105-gene, hybrid-capture, next-generati...

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Autores principales:	Justin D. Finkle, Hala Boulos, Terri M. Driessen, Christine Lo, Richard A. Blidner, Ashraf Hafez, Aly A. Khan, Ariane Lozac’hmeur, Kelly E. McKinnon, Jason Perera, Wei Zhu, Afshin Dowlati, Kevin P. White, Robert Tell, Nike Beaubier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/439e514d758c4462a85579f192a11c43
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spelling	oai:doaj.org-article:439e514d758c4462a85579f192a11c432021-12-02T18:18:43ZValidation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA10.1038/s41698-021-00202-22397-768Xhttps://doaj.org/article/439e514d758c4462a85579f192a11c432021-07-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00202-2https://doaj.org/toc/2397-768XAbstract Liquid biopsy is a valuable precision oncology tool that is increasingly used as a non-invasive approach to identify biomarkers, detect resistance mutations, monitor disease burden, and identify early recurrence. The Tempus xF liquid biopsy assay is a 105-gene, hybrid-capture, next-generation sequencing (NGS) assay that detects single-nucleotide variants, insertions/deletions, copy number variants, and chromosomal rearrangements. Here, we present extensive validation studies of the xF assay using reference standards, cell lines, and patient samples that establish high sensitivity, specificity, and accuracy in variant detection. The Tempus xF assay is highly concordant with orthogonal methods, including ddPCR, tumor tissue-based NGS assays, and another commercial plasma-based NGS assay. Using matched samples, we developed a dynamic filtering method to account for germline mutations and clonal hematopoiesis, while significantly decreasing the number of false-positive variants reported. Additionally, we calculated accurate circulating tumor fraction estimates (ctFEs) using the Off-Target Tumor Estimation Routine (OTTER) algorithm for targeted-panel sequencing. In a cohort of 1,000 randomly selected cancer patients who underwent xF testing, we found that ctFEs correlated with disease burden and clinical outcomes. These results highlight the potential of serial testing to monitor treatment efficacy and disease course, providing strong support for incorporating liquid biopsy in the management of patients with advanced disease.Justin D. FinkleHala BoulosTerri M. DriessenChristine LoRichard A. BlidnerAshraf HafezAly A. KhanAriane Lozac’hmeurKelly E. McKinnonJason PereraWei ZhuAfshin DowlatiKevin P. WhiteRobert TellNike BeaubierNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Justin D. Finkle Hala Boulos Terri M. Driessen Christine Lo Richard A. Blidner Ashraf Hafez Aly A. Khan Ariane Lozac’hmeur Kelly E. McKinnon Jason Perera Wei Zhu Afshin Dowlati Kevin P. White Robert Tell Nike Beaubier Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA
description	Abstract Liquid biopsy is a valuable precision oncology tool that is increasingly used as a non-invasive approach to identify biomarkers, detect resistance mutations, monitor disease burden, and identify early recurrence. The Tempus xF liquid biopsy assay is a 105-gene, hybrid-capture, next-generation sequencing (NGS) assay that detects single-nucleotide variants, insertions/deletions, copy number variants, and chromosomal rearrangements. Here, we present extensive validation studies of the xF assay using reference standards, cell lines, and patient samples that establish high sensitivity, specificity, and accuracy in variant detection. The Tempus xF assay is highly concordant with orthogonal methods, including ddPCR, tumor tissue-based NGS assays, and another commercial plasma-based NGS assay. Using matched samples, we developed a dynamic filtering method to account for germline mutations and clonal hematopoiesis, while significantly decreasing the number of false-positive variants reported. Additionally, we calculated accurate circulating tumor fraction estimates (ctFEs) using the Off-Target Tumor Estimation Routine (OTTER) algorithm for targeted-panel sequencing. In a cohort of 1,000 randomly selected cancer patients who underwent xF testing, we found that ctFEs correlated with disease burden and clinical outcomes. These results highlight the potential of serial testing to monitor treatment efficacy and disease course, providing strong support for incorporating liquid biopsy in the management of patients with advanced disease.
format	article
author	Justin D. Finkle Hala Boulos Terri M. Driessen Christine Lo Richard A. Blidner Ashraf Hafez Aly A. Khan Ariane Lozac’hmeur Kelly E. McKinnon Jason Perera Wei Zhu Afshin Dowlati Kevin P. White Robert Tell Nike Beaubier
author_facet	Justin D. Finkle Hala Boulos Terri M. Driessen Christine Lo Richard A. Blidner Ashraf Hafez Aly A. Khan Ariane Lozac’hmeur Kelly E. McKinnon Jason Perera Wei Zhu Afshin Dowlati Kevin P. White Robert Tell Nike Beaubier
author_sort	Justin D. Finkle
title	Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA
title_short	Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA
title_full	Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA
title_fullStr	Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA
title_full_unstemmed	Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA
title_sort	validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor dna
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/439e514d758c4462a85579f192a11c43
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Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA

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