146: Automated, Decentralized cfDNA Profiling for Targetable and Resistance Alterations

Chan HT et al et al., Clinical Chemistry - This study evaluates an automated, decentralized cfDNA NGS workflow (Oncomine Precision Assay GX with the Genexus system) in 298 patients with advanced solid tumors. The assay achieved 99% sequencing success, detected mut-ctDNA in about half of patients, identified actionable or resistance alterations in 18% of patients, and showed 72% concordance with matched tissue profiling. Detection sensitivity varied by cancer type, tumor burden, and metastatic site, and plasma-only variants were enriched after targeted therapy. Key terms: cell-free DNA, ctDNA, decentralized sequencing, Oncomine Precision Assay, liquid biopsy.

Study Highlights:
An automated point-of-care cfDNA NGS workflow yielded a 99% sequencing success rate and higher success than archived tissue. Approximately 50% of patients had detectable mut-ctDNA and 18% harbored targetable or resistance alterations, with overall tissue–plasma concordance of 72%. Plasma-only alterations (63 events) were found in 18% of patients and were more frequent after targeted therapy; detection sensitivity correlated with tumor fraction, lesion size, cancer type, and metastatic site. Clonal hematopoiesis and limited gene coverage of the assay were notable confounders.

Conclusion:
Automated, decentralized cfDNA genomic profiling is clinically feasible and can expand timely access to actionable genomic data, but results should be interpreted considering tumor burden, metastatic site, prior therapies, and clonal hematopoiesis.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Automated and Decentralized Genomic Profiling of Plasma Cell-Free DNA for Identification of Targetable and Resistance Alterations in Advanced Solid Tumors

First author:
Chan HT et al

Journal:
Clinical Chemistry

DOI:
10.1093/clinchem/hvaf045

Reference:
Chan HT et al. Automated and Decentralized Genomic Profiling of Plasma Cell-Free DNA for Identification of Targetable and Resistance Alterations in Advanced Solid Tumors. Clinical Chemistry 71:6 700–712 (2025). https://doi.org/10.1093/clinchem/hvaf045

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00

Official website https://basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/automated-and-decentralized-genomic-profiling-of-plasma-cell-free-dna-in-solid-tumors

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-09-23.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited transcript sections describing the decentralized cfDNA workflow (OPA GX + Genexus), matched-normal CH filtering, plasma–tissue concordance, cancer-type shedding differences, plasma-only alterations, and complementary tissue testing.
- transcript topics: Foundations of cfDNA/ctDNA and liquid biopsy; Decentralized cfDNA sequencing workflow (OPA GX + Genexus); Clonal hematopoiesis and matched normal filtering; Plasma–tissue concordance and determinants (tumor burden and metastatic site); Plasma-only alterations and resistance evolution; Complementary role of tissue testing and limits of plasma CNV detection

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found:...

Chapters

• (00:00:00) - Decentralized liquid biopsy for advanced cancers
• (00:01:31) - Liquid biopsy vs. tissue profiling
• (00:04:04) - Immunity from the liquid biopsy
• (00:04:49) - The Covance DNA test
• (00:07:23) - The Match Between Tissue and Plasma
• (00:08:13) - The rapid plasma test for cancer...
• (00:11:31) - Plasma only mutations in cancer
• (00:15:05) - Base by base science