Analytical validation of a novel comprehensive genomic profiling informed circulating tumor DNA monitoring assay for solid tumors

Daniel R Zollinger, Elizabeth Rivers, Alexander Fine, Yanmei Huang, Joseph Son, Akshita Kalyan, Wren Gray, Golshid Baharian, Carly Hammond, Rosalyn Ram, Lindsay Ringman, Dina Hafez, Daniel Savel, Vipul Patel, Marc Dantone, Cui Guo, Merrida Childress, Chang Xu, Dorhyun Johng, Brett Wallden, Prapti Pokharel, William Camara, Priti S Hegde, Jason Hughes, Corey Carter, Nicole Davarpanah, Viraj Degaonkar, Pratyush Gupta, Sanjeev Mariathasan, Thomas Powles, Sean Ferree, Lucas Dennis and Amanda Young

PLOS ONE, 2024, vol. 19, issue 5, 1-18

Abstract: Emerging technologies focused on the detection and quantification of circulating tumor DNA (ctDNA) in blood show extensive potential for managing patient treatment decisions, informing risk of recurrence, and predicting response to therapy. Currently available tissue-informed approaches are often limited by the need for additional sequencing of normal tissue or peripheral mononuclear cells to identify non-tumor-derived alterations while tissue-naïve approaches are often limited in sensitivity. Here we present the analytical validation for a novel ctDNA monitoring assay, FoundationOne®Tracker. The assay utilizes somatic alterations from comprehensive genomic profiling (CGP) of tumor tissue. A novel algorithm identifies monitorable alterations with a high probability of being somatic and computationally filters non-tumor-derived alterations such as germline or clonal hematopoiesis variants without the need for sequencing of additional samples. Monitorable alterations identified from tissue CGP are then quantified in blood using a multiplex polymerase chain reaction assay based on the validated SignateraTM assay. The analytical specificity of the plasma workflow is shown to be 99.6% at the sample level. Analytical sensitivity is shown to be >97.3% at ≥5 mean tumor molecules per mL of plasma (MTM/mL) when tested with the most conservative configuration using only two monitorable alterations. The assay also demonstrates high analytical accuracy when compared to liquid biopsy-based CGP as well as high qualitative (measured 100% PPA) and quantitative precision (

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0302129 (text/html)
https://journals.plos.org/plosone/article/file?id= ... 02129&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0302129

DOI: 10.1371/journal.pone.0302129

Access Statistics for this article

More articles in PLOS ONE from Public Library of Science
Bibliographic data for series maintained by plosone ().