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Evaluation of cell-free DNA approaches for multi-cancer early detection

Jamshidi, A; Liu, MC; Klein, EA; Venn, O; Hubbell, E; Beausang, JF; Gross, S; ... Swanton, C; + view all (2022) Evaluation of cell-free DNA approaches for multi-cancer early detection. Cancer Cell , 40 (12) pp. 1537-1549. 10.1016/j.ccell.2022.10.022. Green open access

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Abstract

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approaches. The WG methylation feature best predicts cancer signal origin. WG methylation is the most promising technology for MCED and informs development of a targeted methylation MCED test.

Type: Article
Title: Evaluation of cell-free DNA approaches for multi-cancer early detection
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ccell.2022.10.022
Publisher version: https://doi.org/10.1016/j.ccell.2022.10.022
Language: English
Additional information: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: CCGA, MCED, cancer screening, cfDNA, multi-cancer early detection, single nucleotide variants, somatic copy number alterations, whole-genome bisulfite sequencing, whole-genome methylation, Humans, Cell-Free Nucleic Acids, Early Detection of Cancer, Neoplasms, Biomarkers, Tumor, DNA Methylation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10162940
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